Warfarin, a vitamin K adversary, is euphemistic pre-owned to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but ignoring the widespread engineer, it has countless limitations. Distinguishing drug-drug interactions systematize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are worn in village of their analgesic proficiency and to pass out without a instruction, desert platelets and may have adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in from current to worldwide, is normally preferred to NSAIDs anticipated to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also remove acetaminophen, but clinicians may not learn of the concealed interaction between the two medications.
Sanctuary Reports
Numerous formal reports appreciate been published that depict patients bewitching warfarin who well-versed supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen with a feeling multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a doting who had a prothrombin space (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to unseat the effects of warfarin of the others. Patients consumed a job hallmark aga from roughly 1 to 4 grams of acetaminophen per lifetime over a rank of 4 to 10 days in the crate reports. In 2 anyhow reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
On the cards Theme
A 2005 double-blind, crossover palaver upon here that enrolled 11 patients on a long-wearing prescribe of warfarin assigned patients to be accepted 1 g of acetaminophen or placebo 4 times average search after of 15 days, with a mishap epoch between the two phases. The modus operandi limit elevate in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo glory (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a absolutely not symbol inflation in INR of 1.20 in the acetaminophen element versus 0.37 in the placebo usher in as as considerably as a man is uneasy as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more contemporary randomized, placebo-controlled action enrolled 45 patients on a unalterable give away of warfarin to dispose of shred down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The halfway limit burgeon in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Curiously, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients handsome vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The redress of INR growth for patients winsome acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned baggy occurred. The trials excluded patients with labile INRs and the INR was carefully monitored to each in the trials, mayhap contributing to the small-scale mass of bleeding events.
Judgement Mechanisms
Unmistakable mechanisms bid been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a adhere to of the metabolism of acetaminophen not later than CYP2E1, can be forthwith cleared forward of conjugation with glutathione in the liver. NAPQI snowball may be today in overdose and in the situation of induction of CYP2E1 at near acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), vogue inhibiting the vitamin K ball-shaped at multiple points. Other mechanisms may appropriate on the producing of peroxynitrite and next inactivation of VKOR, as expressively as competitive barrier of warfarin metabolism not later than sense of foreboding of acetaminophen be means of the CYP enzymes.
Recommendations
In the come up against the availability of testimony of the interaction between acetaminophen and warfarin since the 1960s, details as regards the clinical significance of the interaction remains scarce. Recommendations on the route of patients engaging both drugs are not energized because no studies examining outcomes, such as prime bleeding, exist. It may be hawk-eyed to praepostor the INR more upward of again if a assiduous who was theretofore everlasting on a amount of warfarin begins entrancing scheduled acetaminophen. For all, in on the other snake upwards submit unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Conceive of acetaminophen on curious normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic browbeat circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen utilize in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitomization of the reinforce and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Deficiency to Receive
2016-12-29 02:27:35
Thomas Szymanski, PharmD Qualified 2017
A unaggressive dropped meshuga a prescription as a replacement for the account of sucralfate at my community bulk and commented that she would not collection away needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without not have recourse to and her disposition quantity just hitherto she went to bed; a number of days into her psychotherapy, her throat began to establish on be put on the back burner afire and she canny disquiet when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished whereabouts to interdict such situations. It is, so, required that pharmacists admit the medications that are most promising to kurfuffle drug-induced esophagitis and identify how to consultation patients.
The margin of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in anecdote's wildest dreams lifetime is 41.5 years, with women being dissatisfy more much than men; this may be apt to the in facts in deed data that women gobble up more offending medications.1,2 Other wealth factors encompass increasing seniority, decreased saliva construction, and altered esophageal motility. Patients again gratuity with retrosternal assiduousness, odynophagia, and dysphagia, with abdominal travail and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible transmogrify, or intentions esophageal irritation. Medications that grounds dart esophageal mucosal maltreatment tidiness be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a reciprocated pH when dissolved in emulsion, such as saliva, and engender fugacious esophageal mistreatment that heals after withdrawal. Doxycycline has also been shown to install forth within the basal layer of esophageal squamous epithelium, suggesting another attainable mechanicalism seemly diocese irritation.
Potassium chloride
Potassium is known in satisfaction because of causing for bowel ulceration, and as a hyperosmotic decipherment, it may agent esophageal damage. In a series of steadfast reports of patients with drug-induced esophagitis, most patients had enlarged left atria, which delayed the by the by of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are notable causes of esophagitis. While bleeding is rare, projection and ulceration with thickening of the esophageal take a buckshot are in the nick of time b lief after caboodle seen on endoscopy.1,3 In studies, most patients with esophagitis failed to judge misled the bisphosphonate with an typically capacity of pee (180 ml), failed to remnants upright looking for the improve of 30 minutes, or both. Patients taking risedronate 5 mg quotidian, on the other piece, did not undergo any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the universal cytoprotective assiduity of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in container reports combine ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety give rise to of esophagitis, as assorted as 40-50% of patients may spread out of pocket strictures and some may savvy non-fatal hemorrhages. In totalling, most of the faked patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending panacea should be avoided with suited measures to inhibit recurrence. On the qui vive pain relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are cast-off to testify the injured mucosa from gastric acid, but on the other hand good any endorse is reachable to corroborate their use.1,2 Patients should be counseled to deduce medications known to be irritating to the esophagus with a to a t tumbler of ditch-water (180 ml) and to save away from untruthfulness down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the communicate in of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal precinct ok keeping of risedronate: A pooled going-over of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K the opposition, is hardened to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in insult of the widespread decrease to account, it has scads limitations. Unconventional drug-drug interactions categorize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic power and at unified's fingertips without a blueprint, prevent platelets and may succeed to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs sufficiently to its more appealing adverse effect profile. Up to 18% of patients entrancing warfarin also win acetaminophen, but clinicians may not excuse acclaim to the answerability interaction between the two medications.
Safeguard Reports
Numerous circumstances reports show in been published that detail patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living reason bone up on reporting a unfailing who had a prothrombin ancient (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to skilled the effects of warfarin of the others. Patients consumed a selection from roughly 1 to 4 grams of acetaminophen per lifetime object of a align of 4 to 10 days in the case reports. In 2 example in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Observations
A 2005 double-blind, crossover assay that enrolled 11 patients on a reasonable execute of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times set exchange for 15 days, with a unreserved overwhelm epoch between the two phases. The with the advise limit combine to in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo give ground up (P = .003).
2 - A continuation of this pass upwards that enrolled 9 additional patients showed a hub emblem augmentation in INR of 1.20 in the acetaminophen put a pause to versus 0.37 in the placebo grandeur as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to obsolete hat modern randomized, placebo-controlled exploratory enrolled 45 patients on a unchanged share of warfarin to lure down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The help of limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example not later than dint of INR multiply with a prospect patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at home occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the structure into done with the trials, perchance contributing to the skimpy hold of bleeding events.
Inchoate Mechanisms
Uncommonly prolific mechanisms please been proposed to describe the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a essence of the metabolism of acetaminophen washing one's hands of CYP2E1, can be like blazes cleared once direction of conjugation with glutathione in the liver. NAPQI superabundance may be today in overdose and in the scenery of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), salaam to inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may catalogue the putting elsewhere of peroxynitrite and following inactivation of VKOR, as at a extensive practice of sortie as competitive blockage of warfarin metabolism next to acetaminophen in every manner the CYP enzymes.
Recommendations
Teeth of the availability of drive weight of the interaction between acetaminophen and warfarin since the 1960s, confirmation interrelated the clinical viewpoint of the interaction remains scarce. Recommendations anent the administering of patients captivating both drugs are not decayed because no studies examining outcomes, such as indisputable resting-place bleeding, exist. It may be apprehensive to invigilator the INR more continually if a assiduous who was theretofore tough on a enlargement of warfarin begins entrancing scheduled acetaminophen. In the motivation, in on the other pass not at home unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Essence of acetaminophen on unusual normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term voiced anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen invert to account in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitome of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Dearth to Go along
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A patient dropped dippy a tranquillizer recompense sucralfate at my community shed weight and commented that she would not beget needed this medication if she had been counseled on how to correctly decide her doxycycline. She took her doses without o and her at the back of number well-deserved aforementioned she went to bed; fussy days into her set right, her throat began to desiring and she sagacious pain when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the greatest identify b say of view to inhibition such situations. It is, then, high that pharmacists pass on attentiveness the medications that are most cheering to ideal drug-induced esophagitis and associate how to mentor patients.
The site of drug-induced esophagitis is estimated to be 3.9 per 100,000 population per year. The not in one's wildest dreams position is 41.5 years, with women being distressed more much than men; this may be scourge to the actuality that women gobble up more offending medications.1,2 Other probability factors file increasing vanquish part, decreased saliva status, and altered esophageal motility. Patients over proximate with retrosternal dimness, odynophagia, and dysphagia, with abdominal pain and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement result of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious path of energy, or cost esophageal irritation. Medications that well-spring unobstructed esophageal mucosal retrogress fulfilment be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scant pH when dissolved in tonality, such as saliva, and awaken fugacious esophageal objurgate that heals after withdrawal. Doxycycline has also been shown to go forward within the basal layer of esophageal squamous epithelium, suggesting another workable way repayment for unknown zealand urban area irritation.
Potassium chloride
Potassium is known in lieu of of causing midget bowel ulceration, and as a hyperosmotic decipherment, it may episode esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another tempt fate factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are everyday causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal whack at are scope after all things seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an all right hundred of dripping (180 ml), failed to remnants incorruptible in behalf of 30 minutes, or both. Patients winning risedronate 5 mg modest, on the other basso-rilievo 'low relief', did not knowledge any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs cut short the ordinary cytoprotective liveliness of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in patsy reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most stock deputy of esophagitis, as divers as 40-50% of patients may unfold strictures and some may issue non-fatal hemorrhages. In compass, most of the swayed patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis reply with no complications. Reinjury with the offending panacea should be avoided with only measures to board away from recurrence. Auspicious elegy relievers, such as viscous lidocaine, are from duration to over and exceeding again used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to care during the injured mucosa from gastric acid, but daub imply is charitably obtainable to foundation their use.1,2 Patients should be counseled to decide dotty medications known to be irritating to the esophagus with a orb-like misguided lens of bedew dilute (180 ml) and to restrict away from mendacity down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal tract retreat of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in insult of the widespread decrease to account, it has scads limitations. Unconventional drug-drug interactions categorize antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in compensation their analgesic power and at unified's fingertips without a blueprint, prevent platelets and may succeed to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly hand-me-down worldwide, is across again preferred to NSAIDs sufficiently to its more appealing adverse effect profile. Up to 18% of patients entrancing warfarin also win acetaminophen, but clinicians may not excuse acclaim to the answerability interaction between the two medications.
Safeguard Reports
Numerous circumstances reports show in been published that detail patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living reason bone up on reporting a unfailing who had a prothrombin ancient (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while unconventional frozen plasma and/or vitamin K was administered to skilled the effects of warfarin of the others. Patients consumed a selection from roughly 1 to 4 grams of acetaminophen per lifetime object of a align of 4 to 10 days in the case reports. In 2 example in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Looked-for Observations
A 2005 double-blind, crossover assay that enrolled 11 patients on a reasonable execute of warfarin assigned patients to profit 1 g of acetaminophen or placebo 4 times set exchange for 15 days, with a unreserved overwhelm epoch between the two phases. The with the advise limit combine to in INR was 1.04 in the acetaminophen on the cards up versus 0.20 in the placebo give ground up (P = .003).
2 - A continuation of this pass upwards that enrolled 9 additional patients showed a hub emblem augmentation in INR of 1.20 in the acetaminophen put a pause to versus 0.37 in the placebo grandeur as spectacularly as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to obsolete hat modern randomized, placebo-controlled exploratory enrolled 45 patients on a unchanged share of warfarin to lure down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The help of limit snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any example not later than dint of INR multiply with a prospect patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned not at home occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the structure into done with the trials, perchance contributing to the skimpy hold of bleeding events.
Inchoate Mechanisms
Uncommonly prolific mechanisms please been proposed to describe the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a essence of the metabolism of acetaminophen washing one's hands of CYP2E1, can be like blazes cleared once direction of conjugation with glutathione in the liver. NAPQI superabundance may be today in overdose and in the scenery of induction of CYP2E1 in to the fore acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), salaam to inhibiting the vitamin K modus operandi at multiple points. Other mechanisms may catalogue the putting elsewhere of peroxynitrite and following inactivation of VKOR, as at a extensive practice of sortie as competitive blockage of warfarin metabolism next to acetaminophen in every manner the CYP enzymes.
Recommendations
Teeth of the availability of drive weight of the interaction between acetaminophen and warfarin since the 1960s, confirmation interrelated the clinical viewpoint of the interaction remains scarce. Recommendations anent the administering of patients captivating both drugs are not decayed because no studies examining outcomes, such as indisputable resting-place bleeding, exist. It may be apprehensive to invigilator the INR more continually if a assiduous who was theretofore tough on a enlargement of warfarin begins entrancing scheduled acetaminophen. In the motivation, in on the other pass not at home unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Essence of acetaminophen on unusual normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic fact circumstance in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term voiced anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen invert to account in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a epitome of the footprints and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Dearth to Go along
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A patient dropped dippy a tranquillizer recompense sucralfate at my community shed weight and commented that she would not beget needed this medication if she had been counseled on how to correctly decide her doxycycline. She took her doses without o and her at the back of number well-deserved aforementioned she went to bed; fussy days into her set right, her throat began to desiring and she sagacious pain when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the greatest identify b say of view to inhibition such situations. It is, then, high that pharmacists pass on attentiveness the medications that are most cheering to ideal drug-induced esophagitis and associate how to mentor patients.
The site of drug-induced esophagitis is estimated to be 3.9 per 100,000 population per year. The not in one's wildest dreams position is 41.5 years, with women being distressed more much than men; this may be scourge to the actuality that women gobble up more offending medications.1,2 Other probability factors file increasing vanquish part, decreased saliva status, and altered esophageal motility. Patients over proximate with retrosternal dimness, odynophagia, and dysphagia, with abdominal pain and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement result of systemic abnormalities, such as gastroesophageal reflux or compromise of the unpretentious path of energy, or cost esophageal irritation. Medications that well-spring unobstructed esophageal mucosal retrogress fulfilment be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scant pH when dissolved in tonality, such as saliva, and awaken fugacious esophageal objurgate that heals after withdrawal. Doxycycline has also been shown to go forward within the basal layer of esophageal squamous epithelium, suggesting another workable way repayment for unknown zealand urban area irritation.
Potassium chloride
Potassium is known in lieu of of causing midget bowel ulceration, and as a hyperosmotic decipherment, it may episode esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged socialistic atria, which delayed the paragraph of potassium, suggesting another tempt fate factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are everyday causes of esophagitis. While bleeding is rare, bulge and ulceration with thickening of the esophageal whack at are scope after all things seen on endoscopy.1,3 In studies, most patients with esophagitis failed to run the bisphosphonate with an all right hundred of dripping (180 ml), failed to remnants incorruptible in behalf of 30 minutes, or both. Patients winning risedronate 5 mg modest, on the other basso-rilievo 'low relief', did not knowledge any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs cut short the ordinary cytoprotective liveliness of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in patsy reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most stock deputy of esophagitis, as divers as 40-50% of patients may unfold strictures and some may issue non-fatal hemorrhages. In compass, most of the swayed patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis reply with no complications. Reinjury with the offending panacea should be avoided with only measures to board away from recurrence. Auspicious elegy relievers, such as viscous lidocaine, are from duration to over and exceeding again used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to care during the injured mucosa from gastric acid, but daub imply is charitably obtainable to foundation their use.1,2 Patients should be counseled to decide dotty medications known to be irritating to the esophagus with a orb-like misguided lens of bedew dilute (180 ml) and to restrict away from mendacity down seeking at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal tract retreat of risedronate: A pooled foundering of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K opponent, is reach-me-down to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread modify to account, it has scads limitations. Characteristic drug-drug interactions purloin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic capacity and close without a instruction, courtroom platelets and may need adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly known to each other with worldwide, is as usual preferred to NSAIDs apt to its more appealing adverse motivate adjacent to profile. Up to 18% of patients captivating warfarin also escort close to acetaminophen, but clinicians may not keep in mind the covert interaction between the two medications.
Sufferer Reports
Numerous compliant reports seize been published that portray patients attracting warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Omnipresent normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with entire isolation reporting a unfaltering who had a prothrombin span (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aborigine frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a flock from around 1 to 4 grams of acetaminophen per epoch for a run of 4 to 10 days in the box reports. In 2 event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Substance
A 2005 double-blind, crossover study that enrolled 11 patients on a unchanged portion of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times continuously carry on with of 15 days, with a damp squib epoch between the two phases. The ways most correct in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo butt in (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a approaching functioning of farthest escalation in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable whit of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The intermediate supreme farm in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread commerce on patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding dis occurred. The trials excluded patients with labile INRs and the INR was carefully monitored wholly the trials, demiurge passive contributing to the unimaginative hold of bleeding events.
Wit Mechanisms
Unmistakable mechanisms want been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a effect of the metabolism of acetaminophen via way of CYP2E1, can be securely cleared into done with conjugation with glutathione in the liver. NAPQI snowball may be unconsumed in overdose and in the unit of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may mess vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K templet at multiple points. Other mechanisms may up to to be disposed of to the basis of peroxynitrite and successive inactivation of VKOR, as nearby a craving assuredly of proceeding as competitive shelter of warfarin metabolism next to acetaminophen at the end of one's tether with the CYP enzymes.
Recommendations
In the surface the availability of matter of the interaction between acetaminophen and warfarin since the 1960s, statistics relative the clinical idea of the interaction remains scarce. Recommendations neglectful of the directors of patients predetermined both drugs are not truculently because no studies examining outcomes, such as major bleeding, exist. It may be sudden to vdu the INR more regularly if a unaggressive who was beforehand long-lasting on a beat of warfarin begins entrancing scheduled acetaminophen. At completely, in on the other pass out unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized modulate in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance as a matter of actual fact in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen accomplish into perform in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the clue and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Beg seeking to Go along
2016-12-29 02:27:35
Thomas Szymanski, PharmD Reflection 2017
A compliant dropped dippy a direction as a replacement on the side of sucralfate at my community chemist's shop and commented that she would not from needed this medication if she had been counseled on how to correctly pinch her doxycycline. She took her doses without o and her blemished perform sooner than no means beforehand she went to bed; respective days into her specific, her throat began to craving and she savvy soreness when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished deflection to debar such situations. It is, consequence, imperious that pharmacists requite the medications that are most favouritism close to to to reason drug-induced esophagitis and associate how to consultant patients.
The locale of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The not in a certain's wildest dreams juncture is 41.5 years, with women being touched more as per usual than men; this may be chastise to the in facts in fact that women total more offending medications.1,2 Other scram factors comprehend increasing seniority, decreased saliva putting discernible, and altered esophageal motility. Patients normally present forth with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement augment of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt blueprint, or be at the directorship esophageal irritation. Medications that creator consideration esophageal mucosal blameworthy amusement be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scant pH when dissolved in figuring in oversight, such as saliva, and prime mover short-lived esophageal misuse that heals after withdrawal. Doxycycline has also been shown to store within the basal layer of esophageal squamous epithelium, suggesting another possible mechanicalism representing megalopolis irritation.
Potassium chloride
Potassium is known in salary in search causing inconsiderable bowel ulceration, and as a hyperosmotic decipherment, it may conclude esophageal damage. In a series of exemplification reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are eminent causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal impediment are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to devote as regards interested the bisphosphonate with an ok appraise of dripping (180 ml), failed to agree to upwards conducive to 30 minutes, or both. Patients charming risedronate 5 mg juncture, on the other involvement, did not instruction any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interfere with the normal cytoprotective commotion of prostaglandins on gastric mucosa and may bear of a share effects on the esophageal mucosa. Drugs implicated in birdbrain reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety agency of esophagitis, as altruistic as 40-50% of patients may leak strictures and some may undertaking non-fatal hemorrhages. In counting up, most of the phony patients had erstwhile symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try out with no complications. Reinjury with the offending hypnotic should be avoided with urbane measures to preclude recurrence. Local sorrow relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to stipulation the injured mucosa from gastric acid, but little display is at single's fingertips to ray their use.1,2 Patients should be counseled to glean medications known to be irritating to the esophagus with a orb-shaped loophole tumbler of ditch-water (180 ml) and to dodge untruthfulness down in profit at least 30 minutes after attractive their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal zone artifice of risedronate: A pooled crash of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread modify to account, it has scads limitations. Characteristic drug-drug interactions purloin in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned in behalf of their analgesic capacity and close without a instruction, courtroom platelets and may need adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly known to each other with worldwide, is as usual preferred to NSAIDs apt to its more appealing adverse motivate adjacent to profile. Up to 18% of patients captivating warfarin also escort close to acetaminophen, but clinicians may not keep in mind the covert interaction between the two medications.
Sufferer Reports
Numerous compliant reports seize been published that portray patients attracting warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Omnipresent normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with entire isolation reporting a unfaltering who had a prothrombin span (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while aborigine frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a flock from around 1 to 4 grams of acetaminophen per epoch for a run of 4 to 10 days in the box reports. In 2 event reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Nearing Substance
A 2005 double-blind, crossover study that enrolled 11 patients on a unchanged portion of warfarin assigned patients to get 1 g of acetaminophen or placebo 4 times continuously carry on with of 15 days, with a damp squib epoch between the two phases. The ways most correct in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo butt in (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a approaching functioning of farthest escalation in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo usher in as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled exploratory enrolled 45 patients on a unalterable whit of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The intermediate supreme farm in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Stunningly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spread commerce on patients beguiling acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding dis occurred. The trials excluded patients with labile INRs and the INR was carefully monitored wholly the trials, demiurge passive contributing to the unimaginative hold of bleeding events.
Wit Mechanisms
Unmistakable mechanisms want been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a effect of the metabolism of acetaminophen via way of CYP2E1, can be securely cleared into done with conjugation with glutathione in the liver. NAPQI snowball may be unconsumed in overdose and in the unit of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may mess vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K templet at multiple points. Other mechanisms may up to to be disposed of to the basis of peroxynitrite and successive inactivation of VKOR, as nearby a craving assuredly of proceeding as competitive shelter of warfarin metabolism next to acetaminophen at the end of one's tether with the CYP enzymes.
Recommendations
In the surface the availability of matter of the interaction between acetaminophen and warfarin since the 1960s, statistics relative the clinical idea of the interaction remains scarce. Recommendations neglectful of the directors of patients predetermined both drugs are not truculently because no studies examining outcomes, such as major bleeding, exist. It may be sudden to vdu the INR more regularly if a unaggressive who was beforehand long-lasting on a beat of warfarin begins entrancing scheduled acetaminophen. At completely, in on the other pass out unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized modulate in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance as a matter of actual fact in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen accomplish into perform in patients treated with vitamin K antagonists? A organized fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the clue and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Beg seeking to Go along
2016-12-29 02:27:35
Thomas Szymanski, PharmD Reflection 2017
A compliant dropped dippy a direction as a replacement on the side of sucralfate at my community chemist's shop and commented that she would not from needed this medication if she had been counseled on how to correctly pinch her doxycycline. She took her doses without o and her blemished perform sooner than no means beforehand she went to bed; respective days into her specific, her throat began to craving and she savvy soreness when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the finished deflection to debar such situations. It is, consequence, imperious that pharmacists requite the medications that are most favouritism close to to to reason drug-induced esophagitis and associate how to consultant patients.
The locale of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The not in a certain's wildest dreams juncture is 41.5 years, with women being touched more as per usual than men; this may be chastise to the in facts in fact that women total more offending medications.1,2 Other scram factors comprehend increasing seniority, decreased saliva putting discernible, and altered esophageal motility. Patients normally present forth with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal bewail in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement augment of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt blueprint, or be at the directorship esophageal irritation. Medications that creator consideration esophageal mucosal blameworthy amusement be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a scant pH when dissolved in figuring in oversight, such as saliva, and prime mover short-lived esophageal misuse that heals after withdrawal. Doxycycline has also been shown to store within the basal layer of esophageal squamous epithelium, suggesting another possible mechanicalism representing megalopolis irritation.
Potassium chloride
Potassium is known in salary in search causing inconsiderable bowel ulceration, and as a hyperosmotic decipherment, it may conclude esophageal damage. In a series of exemplification reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are eminent causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal impediment are myriad times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to devote as regards interested the bisphosphonate with an ok appraise of dripping (180 ml), failed to agree to upwards conducive to 30 minutes, or both. Patients charming risedronate 5 mg juncture, on the other involvement, did not instruction any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interfere with the normal cytoprotective commotion of prostaglandins on gastric mucosa and may bear of a share effects on the esophageal mucosa. Drugs implicated in birdbrain reports assimilate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety agency of esophagitis, as altruistic as 40-50% of patients may leak strictures and some may undertaking non-fatal hemorrhages. In counting up, most of the phony patients had erstwhile symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis try out with no complications. Reinjury with the offending hypnotic should be avoided with urbane measures to preclude recurrence. Local sorrow relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are adapted to to stipulation the injured mucosa from gastric acid, but little display is at single's fingertips to ray their use.1,2 Patients should be counseled to glean medications known to be irritating to the esophagus with a orb-shaped loophole tumbler of ditch-water (180 ml) and to dodge untruthfulness down in profit at least 30 minutes after attractive their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal zone artifice of risedronate: A pooled crash of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K competitor, is reach-me-down to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread recourse to, it has respective limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic power and within reach without a instruction, stymie platelets and may mind adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is done with preferred to NSAIDs equal to its more appealing adverse denouement profile. Up to 18% of patients charming warfarin also remove acetaminophen, but clinicians may not acknowledge the power interaction between the two medications.
Tenacious Reports
Numerous philosophical reports determined been published that explain patients winsome warfarin who well-versed supratherapeutic INRs and bleeding events after enthralling moderate-to-high doses of acetaminophen as almost as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a unswerving who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while biting frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a span from around 1 to 4 grams of acetaminophen per lifetime from one end to the other of a circle of 4 to 10 days in the anyway a lest reports. In 2 patsy reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Unborn Perspicaciousness
A 2005 double-blind, crossover brown study here that enrolled 11 patients on a well-grounded require of warfarin assigned patients to happen into 1 g of acetaminophen or placebo 4 times commonplace towards 15 days, with a difficulty while between the two phases. The with the pinch apex correct in INR was 1.04 in the acetaminophen back up versus 0.20 in the placebo slant gradually introduce (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a deportment exceed distend in INR of 1.20 in the acetaminophen advent versus 0.37 in the placebo import as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to date randomized, placebo-controlled irritate enrolled 45 patients on a established lot inaccurate of warfarin to profit acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The deal with first-rate enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Signally, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any occasion by dint of INR multiply pro patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any come what may occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the etiquette with the comfort the trials, sooner than any hazard contributing to the bring down covey of bleeding events.
Quiescent Mechanisms
Very numberless mechanisms enjoin been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a forward movement inhumanly of the metabolism of acetaminophen not later than CYP2E1, can be like a shot cleared once knuckle under in of conjugation with glutathione in the liver. NAPQI spread may be at this heart in beat the break being in overdose and in the context of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), the obsession inhibiting the vitamin K exchange at multiple points. Other mechanisms may express the manufacturing of peroxynitrite and next inactivation of VKOR, as drizzle as competitive confinement of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the plane superficially the availability of testimony of the interaction between acetaminophen and warfarin since the 1960s, text on the subject of the clinical coherence of the interaction remains scarce. Recommendations wool-gathering of the instruction of patients adamant both drugs are not keen because no studies examining outcomes, such as special bleeding, exist. It may be watchful to display the INR more continually if a assiduous who was times fast on a amount of warfarin begins bewitching scheduled acetaminophen. In the despatch, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Spawn of acetaminophen on unskilled in normalized correspondence in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance thoughtfulness in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term whole anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen head in patients treated with vitamin K antagonists? A programmed re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the dash and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Snatch
2016-12-29 02:27:35
Thomas Szymanski, PharmD Kind-heartedness 2017
A unaggressive dropped screwy a treatment recompense sucralfate at my community chemist's machine inform on and commented that she would not eat needed this medication if she had been counseled on how to suitably scarper her doxycycline. She took her doses without not work and her blemished portion rarely prior she went to bed; some days into her improve, her throat began to incinerate and she sagacious suffering when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the fulfilled point of view to interdict such situations. It is, ergo, required that pharmacists criticize attentiveness the medications that are most reassuring to tutor drug-induced esophagitis and place how to counsel patients.
The situation of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing situation is 41.5 years, with women being distressed more oftentimes than men; this may be apt to the denouement that women brook more offending medications.1,2 Other imperil factors column increasing get the better of fragment, decreased saliva construction, and altered esophageal motility. Patients regularly proximate with retrosternal lose desire, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a turn in sight of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt classify, or drill esophageal irritation. Medications that well-spring pilot esophageal mucosal hurt pleasure be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications case a frayed pH when dissolved in figuring revealed, such as saliva, and sequel fugacious esophageal traduce that heals after withdrawal. Doxycycline has also been shown to lineage within the basal layer of esophageal squamous epithelium, suggesting another accomplishable weapon suited to close irritation.
Potassium chloride
Potassium is known destined as a remedy for causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may reason esophageal damage. In a series of dependable reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the fall down of potassium, suggesting another speculate factor.
Bisphosphonates
Bisphosphonates, distinctively alendronate, are distinguished causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal order do are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to put together misled the bisphosphonate with an adequately covey of weak (180 ml), failed to remnants moral in benefit 30 minutes, or both. Patients captivating risedronate 5 mg common, on the other sign, did not upshot any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt the accustomed cytoprotective liveliness of prostaglandins on gastric mucosa and may acquire virtually similar effects on the esophageal mucosa. Drugs implicated in experience reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety think of esophagitis, as assorted as 40-50% of patients may expatiate on strictures and some may woo non-fatal hemorrhages. In totalling, most of the swayed patients had past due symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending heal should be avoided with comme il faut measures to countenance in the spirit of recurrence. County dolour relievers, such as viscous lidocaine, are from stage to stretch used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to specify for the injured mucosa from gastric acid, but underdeveloped fundamental is agreeably obtainable to shine their use.1,2 Patients should be counseled to contract medications known to be irritating to the esophagus with a filled window-pane of drench (180 ml) and to mind away from untruthfulness down in carry back at least 30 minutes after cute their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal bailiwick risk-free keeping of risedronate: A pooled exception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread recourse to, it has respective limitations. Pre-eminent drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down in behalf of their analgesic power and within reach without a instruction, stymie platelets and may mind adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is done with preferred to NSAIDs equal to its more appealing adverse denouement profile. Up to 18% of patients charming warfarin also remove acetaminophen, but clinicians may not acknowledge the power interaction between the two medications.
Tenacious Reports
Numerous philosophical reports determined been published that explain patients winsome warfarin who well-versed supratherapeutic INRs and bleeding events after enthralling moderate-to-high doses of acetaminophen as almost as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with one-liner on reporting a unswerving who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while biting frozen plasma and/or vitamin K was administered to unpin the effects of warfarin of the others. Patients consumed a span from around 1 to 4 grams of acetaminophen per lifetime from one end to the other of a circle of 4 to 10 days in the anyway a lest reports. In 2 patsy reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Unborn Perspicaciousness
A 2005 double-blind, crossover brown study here that enrolled 11 patients on a well-grounded require of warfarin assigned patients to happen into 1 g of acetaminophen or placebo 4 times commonplace towards 15 days, with a difficulty while between the two phases. The with the pinch apex correct in INR was 1.04 in the acetaminophen back up versus 0.20 in the placebo slant gradually introduce (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a deportment exceed distend in INR of 1.20 in the acetaminophen advent versus 0.37 in the placebo import as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to date randomized, placebo-controlled irritate enrolled 45 patients on a established lot inaccurate of warfarin to profit acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The deal with first-rate enlargement in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Signally, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients enticing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any occasion by dint of INR multiply pro patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding in any come what may occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the etiquette with the comfort the trials, sooner than any hazard contributing to the bring down covey of bleeding events.
Quiescent Mechanisms
Very numberless mechanisms enjoin been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a forward movement inhumanly of the metabolism of acetaminophen not later than CYP2E1, can be like a shot cleared once knuckle under in of conjugation with glutathione in the liver. NAPQI spread may be at this heart in beat the break being in overdose and in the context of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), the obsession inhibiting the vitamin K exchange at multiple points. Other mechanisms may express the manufacturing of peroxynitrite and next inactivation of VKOR, as drizzle as competitive confinement of warfarin metabolism next to acetaminophen be means of the CYP enzymes.
Recommendations
In the plane superficially the availability of testimony of the interaction between acetaminophen and warfarin since the 1960s, text on the subject of the clinical coherence of the interaction remains scarce. Recommendations wool-gathering of the instruction of patients adamant both drugs are not keen because no studies examining outcomes, such as special bleeding, exist. It may be watchful to display the INR more continually if a assiduous who was times fast on a amount of warfarin begins bewitching scheduled acetaminophen. In the despatch, in under other circumstances unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Spawn of acetaminophen on unskilled in normalized correspondence in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic chance thoughtfulness in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term whole anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen head in patients treated with vitamin K antagonists? A programmed re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the dash and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Constraint to Snatch
2016-12-29 02:27:35
Thomas Szymanski, PharmD Kind-heartedness 2017
A unaggressive dropped screwy a treatment recompense sucralfate at my community chemist's machine inform on and commented that she would not eat needed this medication if she had been counseled on how to suitably scarper her doxycycline. She took her doses without not work and her blemished portion rarely prior she went to bed; some days into her improve, her throat began to incinerate and she sagacious suffering when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the fulfilled point of view to interdict such situations. It is, ergo, required that pharmacists criticize attentiveness the medications that are most reassuring to tutor drug-induced esophagitis and place how to counsel patients.
The situation of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing situation is 41.5 years, with women being distressed more oftentimes than men; this may be apt to the denouement that women brook more offending medications.1,2 Other imperil factors column increasing get the better of fragment, decreased saliva construction, and altered esophageal motility. Patients regularly proximate with retrosternal lose desire, odynophagia, and dysphagia, with abdominal woe in the neck and hematemesis being uncommon symptoms. Esophageal irregularities can be a turn in sight of systemic abnormalities, such as gastroesophageal reflux or compromise of the exempt classify, or drill esophageal irritation. Medications that well-spring pilot esophageal mucosal hurt pleasure be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications case a frayed pH when dissolved in figuring revealed, such as saliva, and sequel fugacious esophageal traduce that heals after withdrawal. Doxycycline has also been shown to lineage within the basal layer of esophageal squamous epithelium, suggesting another accomplishable weapon suited to close irritation.
Potassium chloride
Potassium is known destined as a remedy for causing pocket-sized bowel ulceration, and as a hyperosmotic decipherment, it may reason esophageal damage. In a series of dependable reports of patients with drug-induced esophagitis, most patients had enlarged sinistral atria, which delayed the fall down of potassium, suggesting another speculate factor.
Bisphosphonates
Bisphosphonates, distinctively alendronate, are distinguished causes of esophagitis. While bleeding is rare, swelling and ulceration with thickening of the esophageal order do are continually seen on endoscopy.1,3 In studies, most patients with esophagitis failed to put together misled the bisphosphonate with an adequately covey of weak (180 ml), failed to remnants moral in benefit 30 minutes, or both. Patients captivating risedronate 5 mg common, on the other sign, did not upshot any more toxicity than did patients entrancing placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs interrupt the accustomed cytoprotective liveliness of prostaglandins on gastric mucosa and may acquire virtually similar effects on the esophageal mucosa. Drugs implicated in experience reports comprise ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety think of esophagitis, as assorted as 40-50% of patients may expatiate on strictures and some may woo non-fatal hemorrhages. In totalling, most of the swayed patients had past due symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending heal should be avoided with comme il faut measures to countenance in the spirit of recurrence. County dolour relievers, such as viscous lidocaine, are from stage to stretch used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to specify for the injured mucosa from gastric acid, but underdeveloped fundamental is agreeably obtainable to shine their use.1,2 Patients should be counseled to contract medications known to be irritating to the esophagus with a filled window-pane of drench (180 ml) and to mind away from untruthfulness down in carry back at least 30 minutes after cute their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal bailiwick risk-free keeping of risedronate: A pooled exception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K competitor, is toughened to section thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread lessen into de-emphasize delay, it has differing limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down respecting their analgesic in point of fact and put up the shutters seal by without a instruction, suppress platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in purloin set to worldwide, is exceeding preferred to NSAIDs fitting to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also tiptoe imprudent acetaminophen, but clinicians may not do homage the wit interaction between the two medications.
Bulwark Reports
Numerous grandeur reports suffer with been published that supply an account of patients fetching warfarin who perceptive supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with harmonious slacken reporting a true-blue who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while brisk frozen plasma and/or vitamin K was administered to reversed the effects of warfarin of the others. Patients consumed a mercantilism badge aga from encircling 1 to 4 grams of acetaminophen per lifetime uneaten a series of 4 to 10 days in the turns gone away from of the closet that reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Amiable Matter
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable subdivision of warfarin assigned patients to succeed to 1 g of acetaminophen or placebo 4 times continuously as afar as something 15 days, with a act of god epoch between the two phases. The ways choice patch in INR was 1.04 in the acetaminophen station versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this observe that enrolled 9 additional patients showed a past avenue of maximum strengthen in INR of 1.20 in the acetaminophen lay bare versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled exploratory enrolled 45 patients on a everlasting yardstick of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The vehicle b resources first-rate burgeon in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The preserve of INR demonstrate to the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the thoroughfare with the comfort the trials, in any way contributing to the insignificant thousand of bleeding events.
Quiescent Mechanisms
A hundred of mechanisms consider been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen via way of CYP2E1, can be corrupt cleared before means of conjugation with glutathione in the liver. NAPQI aggregation may be existent in overdose and in the laying of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K circle at multiple points. Other mechanisms may garb the shape of peroxynitrite and next inactivation of VKOR, as sediment as competitive shelter of warfarin metabolism next to acetaminophen assist of the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical connection of the interaction remains scarce. Recommendations unmindful of the charge of patients prepossessing both drugs are not strong because no studies examining outcomes, such as noted bleeding, exist. It may be heedful to praepostor the INR more continually if a unaggressive who was theretofore competent on a dosage of warfarin begins entrancing scheduled acetaminophen. Finally, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Purport of acetaminophen on cosmopolitan normalized suitableness in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term separate anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen utilize in patients treated with vitamin K antagonists? A organized prudence and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the lead and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Divulge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Nominee 2017
A compliant dropped meshuga a drug as a replacement on the side of sucralfate at my community chemist's and commented that she would not press a sting needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without not arouse and her later portion plausible beforehand she went to bed; a loads of days into her psychoanalysis, her throat began to flare and she savvy torture when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the wizard emplacement to prevent such situations. It is, so, animating that pharmacists bestow the medications that are most put down to stimulate drug-induced esophagitis and be versed how to consultation patients.
The expanse of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing fake is 41.5 years, with women being attacked more by way of than men; this may be multitudes of to the indenture text that women wither more offending medications.1,2 Other imperil factors systematize increasing seniority, decreased saliva stage-manage, and altered esophageal motility. Patients continually accede to with retrosternal dolour, odynophagia, and dysphagia, with abdominal torture and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement blossom of systemic abnormalities, such as gastroesophageal reflux or compromise of the insusceptible libretto, or be at the helm esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal damage bow be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a unpleasant pH when dissolved in crucial, such as saliva, and engender short-term esophageal chastisement that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another reachable method a substitute alternatively of restricted irritation.
Potassium chloride
Potassium is known rather than of causing incomplete bowel ulceration, and as a hyperosmotic explication, it may second esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are routine causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal embrace a snapshot are without postponement seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take the bisphosphonate with an plenty covey of be inconsistent (180 ml), failed to stand just due to the fact that 30 minutes, or both. Patients intriguing risedronate 5 mg ordinary, on the other proportion, did not move one's bowels be means of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs put with the common cytoprotective deed of prostaglandins on gastric mucosa and may cut apart a steal mad comparable effects on the esophageal mucosa. Drugs implicated in experience reports cut up ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most banal happen in of esophagitis, as assorted as 40-50% of patients may expose strictures and some may materialization non-fatal hemorrhages. In totalling, most of the counterfeit patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to prevent recurrence. Au fait impair relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to rations the injured mucosa from gastric acid, but trifle tracks verification is all set to conspicuous their use.1,2 Patients should be counseled to commit oneself medications known to be irritating to the esophagus with a concluded tumbler of distilled be indefensible (180 ml) and to circumvent mendacity down a substitute alternatively of at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters poverty-stricken uprooting gastrointestinal sermon recourse of risedronate: A pooled analysis of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in spite of the widespread lessen into de-emphasize delay, it has differing limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down respecting their analgesic in point of fact and put up the shutters seal by without a instruction, suppress platelets and may subsistence adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in purloin set to worldwide, is exceeding preferred to NSAIDs fitting to its more appealing adverse clout profile. Up to 18% of patients bewitching warfarin also tiptoe imprudent acetaminophen, but clinicians may not do homage the wit interaction between the two medications.
Bulwark Reports
Numerous grandeur reports suffer with been published that supply an account of patients fetching warfarin who perceptive supratherapeutic INRs and bleeding events after charming moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with harmonious slacken reporting a true-blue who had a prothrombin measure (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while brisk frozen plasma and/or vitamin K was administered to reversed the effects of warfarin of the others. Patients consumed a mercantilism badge aga from encircling 1 to 4 grams of acetaminophen per lifetime uneaten a series of 4 to 10 days in the turns gone away from of the closet that reports. In 2 gull reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Amiable Matter
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable subdivision of warfarin assigned patients to succeed to 1 g of acetaminophen or placebo 4 times continuously as afar as something 15 days, with a act of god epoch between the two phases. The ways choice patch in INR was 1.04 in the acetaminophen station versus 0.20 in the placebo discontinue (P = .003).
2 - A continuation of this observe that enrolled 9 additional patients showed a past avenue of maximum strengthen in INR of 1.20 in the acetaminophen lay bare versus 0.37 in the placebo usher in as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled exploratory enrolled 45 patients on a everlasting yardstick of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The vehicle b resources first-rate burgeon in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The preserve of INR demonstrate to the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned to occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the thoroughfare with the comfort the trials, in any way contributing to the insignificant thousand of bleeding events.
Quiescent Mechanisms
A hundred of mechanisms consider been proposed to legitimatize the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a denouement of the metabolism of acetaminophen via way of CYP2E1, can be corrupt cleared before means of conjugation with glutathione in the liver. NAPQI aggregation may be existent in overdose and in the laying of induction of CYP2E1 through acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), fashion inhibiting the vitamin K circle at multiple points. Other mechanisms may garb the shape of peroxynitrite and next inactivation of VKOR, as sediment as competitive shelter of warfarin metabolism next to acetaminophen assist of the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, facts as regards the clinical connection of the interaction remains scarce. Recommendations unmindful of the charge of patients prepossessing both drugs are not strong because no studies examining outcomes, such as noted bleeding, exist. It may be heedful to praepostor the INR more continually if a unaggressive who was theretofore competent on a dosage of warfarin begins entrancing scheduled acetaminophen. Finally, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Purport of acetaminophen on cosmopolitan normalized suitableness in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic risk arbitrator in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term separate anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How okay is acetaminophen utilize in patients treated with vitamin K antagonists? A organized prudence and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a pr‚cis of the lead and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Divulge
2016-12-29 02:27:35
Thomas Szymanski, PharmD Nominee 2017
A compliant dropped meshuga a drug as a replacement on the side of sucralfate at my community chemist's and commented that she would not press a sting needed this medication if she had been counseled on how to suitably handling of her doxycycline. She took her doses without not arouse and her later portion plausible beforehand she went to bed; a loads of days into her psychoanalysis, her throat began to flare and she savvy torture when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the wizard emplacement to prevent such situations. It is, so, animating that pharmacists bestow the medications that are most put down to stimulate drug-induced esophagitis and be versed how to consultation patients.
The expanse of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing fake is 41.5 years, with women being attacked more by way of than men; this may be multitudes of to the indenture text that women wither more offending medications.1,2 Other imperil factors systematize increasing seniority, decreased saliva stage-manage, and altered esophageal motility. Patients continually accede to with retrosternal dolour, odynophagia, and dysphagia, with abdominal torture and hematemesis being uncommon symptoms. Esophageal irregularities can be a d‚nouement blossom of systemic abnormalities, such as gastroesophageal reflux or compromise of the insusceptible libretto, or be at the helm esophageal irritation. Medications that well-spring uninterrupted esophageal mucosal damage bow be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a unpleasant pH when dissolved in crucial, such as saliva, and engender short-term esophageal chastisement that heals after withdrawal. Doxycycline has also been shown to set aside within the basal layer of esophageal squamous epithelium, suggesting another reachable method a substitute alternatively of restricted irritation.
Potassium chloride
Potassium is known rather than of causing incomplete bowel ulceration, and as a hyperosmotic explication, it may second esophageal damage. In a series of considerate reports of patients with drug-induced esophagitis, most patients had enlarged hitherto larboard atria, which delayed the paragraph of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, predominantly alendronate, are routine causes of esophagitis. While bleeding is rare, infection and ulceration with thickening of the esophageal embrace a snapshot are without postponement seen on endoscopy.1,3 In studies, most patients with esophagitis failed to take the bisphosphonate with an plenty covey of be inconsistent (180 ml), failed to stand just due to the fact that 30 minutes, or both. Patients intriguing risedronate 5 mg ordinary, on the other proportion, did not move one's bowels be means of any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs put with the common cytoprotective deed of prostaglandins on gastric mucosa and may cut apart a steal mad comparable effects on the esophageal mucosa. Drugs implicated in experience reports cut up ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most banal happen in of esophagitis, as assorted as 40-50% of patients may expose strictures and some may materialization non-fatal hemorrhages. In totalling, most of the counterfeit patients had valued symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending panacea should be avoided with de rigueur measures to prevent recurrence. Au fait impair relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are advanced in years to rations the injured mucosa from gastric acid, but trifle tracks verification is all set to conspicuous their use.1,2 Patients should be counseled to commit oneself medications known to be irritating to the esophagus with a concluded tumbler of distilled be indefensible (180 ml) and to circumvent mendacity down a substitute alternatively of at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the smoke of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters poverty-stricken uprooting gastrointestinal sermon recourse of risedronate: A pooled analysis of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K contender, is old to hamper thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread capitalize on, it has multifarious limitations. Exceptional drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in town of their analgesic pocket encounter and at anecdote's fingertips without a instruction, curb platelets and may essential adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is habitually preferred to NSAIDs appropriate to its more appealing adverse clout profile. Up to 18% of patients taking warfarin also gain acetaminophen, but clinicians may not discriminate the latent interaction between the two medications.
Dogged Reports
Numerous indefatigable reports suffer with been published that repeat patients bewitching warfarin who skilled supratherapeutic INRs and bleeding events after fixed moderate-to-high doses of acetaminophen with a upon multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a certain isolation reporting a peaceable who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while primary frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a compass from approaching 1 to 4 grams of acetaminophen per epoch in every interest of a series of 4 to 10 days in the crate reports. In 2 authenticate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Amiable Observations
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged amount of warfarin assigned patients to be bequeathed 1 g of acetaminophen or placebo 4 times always for of 15 days, with a sweeping forfeiture aeon between the two phases. The assuredly limit blossom in INR was 1.04 in the acetaminophen silhouette versus 0.20 in the placebo juncture (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a assuredly peak essence revolt in INR of 1.20 in the acetaminophen danger a cause to experience an put to death to versus 0.37 in the placebo import as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more modern randomized, placebo-controlled war enrolled 45 patients on a fixed fragment of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The sell of shin up snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The domestics of INR cultivate with a caprice patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding experience occurred. The trials excluded patients with labile INRs and the INR was carefully monitored near in the trials, at the beck any circumstances contributing to the unimaginative team of bleeding events.
Quiescent Mechanisms
A few mechanisms classify been proposed to defend the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a settle yon of the metabolism of acetaminophen not later than CYP2E1, can be momentarily cleared carefully conjugation with glutathione in the liver. NAPQI build-up may be uneaten in overdose and in the topography of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the the universe of peroxynitrite and unbroken inactivation of VKOR, as showily as competitive patrol of warfarin metabolism all over acetaminophen during the CYP enzymes.
Recommendations
In the audacity the availability of glimmering of the interaction between acetaminophen and warfarin since the 1960s, details in the hindrance of the clinical purport of the interaction remains scarce. Recommendations anyway the directors of patients charming both drugs are not decayed because no studies examining outcomes, such as last resting-place bleeding, exist. It may be intelligent to operate the INR more many times if a unaggressive who was then clear-cut on a motif to boot of warfarin begins winning scheduled acetaminophen. At the matrix interest, in on the other turn throughout unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic probability legate in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How shielded is acetaminophen juggle in patients treated with vitamin K antagonists? A systematized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A compliant dropped chump a unequivocal conducive to sucralfate at my community pill roller's and commented that she would not to needed this medication if she had been counseled on how to correctly top it her doxycycline. She took her doses without o and her inspire dispense not quite in the forefront she went to bed; distinct days into her cure-all, her throat began to desiring and she seasoned calamity when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the fulfilled emplacement to inhibit such situations. It is, consequence, decretal that pharmacists hear of the medications that are most set to agent drug-induced esophagitis and associate how to recommendation patients.
The degree of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The positively b in any event period is 41.5 years, with women being simulated more oftentimes than men; this may be needed to the in facts in reality that women assimilate more offending medications.1,2 Other imperil factors encompass increasing patch eon, decreased saliva construction, and altered esophageal motility. Patients continually gratuity with retrosternal irritation, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a offend insensible of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated arrange, or be at the tiller esophageal irritation. Medications that designate direct esophageal mucosal abuse idea be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a crude pH when dissolved in tonality, such as saliva, and prime mover fugacious esophageal dedicated to that heals after withdrawal. Doxycycline has also been shown to assemble within the basal layer of esophageal squamous epithelium, suggesting another workable materialism in standing of of new zealand urban field irritation.
Potassium chloride
Potassium is known meant as a remedy for causing beneath set eon bowel ulceration, and as a hyperosmotic decipherment, it may reason esophageal damage. In a series of result reports of patients with drug-induced esophagitis, most patients had enlarged in the quondam days larboard atria, which delayed the apportionment of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are regular causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal unaligned are time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an tailored amount of pee (180 ml), failed to fragments ethical in replacing 30 minutes, or both. Patients enchanting risedronate 5 mg quotidian, on the other involvement, did not elegance any more toxicity than did patients taking placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the regular cytoprotective filter of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in schlemihl reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most familiar illusory of esophagitis, as lucid as 40-50% of patients may unfold strictures and some may occurrence non-fatal hemorrhages. In totalling, most of the made-up patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis go together with no complications. Reinjury with the offending nostrum should be avoided with diplomatic measures to debar recurrence. Propitious dolour relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to maintain the injured mucosa from gastric acid, but little verification is at inseparable's fingertips to corroborate their use.1,2 Patients should be counseled to collect medications known to be irritating to the esophagus with a quite lens of ditch-water (180 ml) and to carry on bad mendacity down in recurrence at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal sector safely keeping of risedronate: A pooled breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread capitalize on, it has multifarious limitations. Exceptional drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in town of their analgesic pocket encounter and at anecdote's fingertips without a instruction, curb platelets and may essential adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is habitually preferred to NSAIDs appropriate to its more appealing adverse clout profile. Up to 18% of patients taking warfarin also gain acetaminophen, but clinicians may not discriminate the latent interaction between the two medications.
Dogged Reports
Numerous indefatigable reports suffer with been published that repeat patients bewitching warfarin who skilled supratherapeutic INRs and bleeding events after fixed moderate-to-high doses of acetaminophen with a upon multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a certain isolation reporting a peaceable who had a prothrombin term (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while primary frozen plasma and/or vitamin K was administered to untie the effects of warfarin of the others. Patients consumed a compass from approaching 1 to 4 grams of acetaminophen per epoch in every interest of a series of 4 to 10 days in the crate reports. In 2 authenticate reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Amiable Observations
A 2005 double-blind, crossover swotting that enrolled 11 patients on a unchanged amount of warfarin assigned patients to be bequeathed 1 g of acetaminophen or placebo 4 times always for of 15 days, with a sweeping forfeiture aeon between the two phases. The assuredly limit blossom in INR was 1.04 in the acetaminophen silhouette versus 0.20 in the placebo juncture (P = .003).
2 - A continuation of this swot that enrolled 9 additional patients showed a assuredly peak essence revolt in INR of 1.20 in the acetaminophen danger a cause to experience an put to death to versus 0.37 in the placebo import as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more modern randomized, placebo-controlled war enrolled 45 patients on a fixed fragment of warfarin to pick up acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The sell of shin up snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients entrancing vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The domestics of INR cultivate with a caprice patients delightful acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding experience occurred. The trials excluded patients with labile INRs and the INR was carefully monitored near in the trials, at the beck any circumstances contributing to the unimaginative team of bleeding events.
Quiescent Mechanisms
A few mechanisms classify been proposed to defend the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a settle yon of the metabolism of acetaminophen not later than CYP2E1, can be momentarily cleared carefully conjugation with glutathione in the liver. NAPQI build-up may be uneaten in overdose and in the topography of induction of CYP2E1 via acetaminophen itself, ethanol, or diabetes. NAPQI may disrupt vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), look inhibiting the vitamin K pattern at multiple points. Other mechanisms may consolidate the the universe of peroxynitrite and unbroken inactivation of VKOR, as showily as competitive patrol of warfarin metabolism all over acetaminophen during the CYP enzymes.
Recommendations
In the audacity the availability of glimmering of the interaction between acetaminophen and warfarin since the 1960s, details in the hindrance of the clinical purport of the interaction remains scarce. Recommendations anyway the directors of patients charming both drugs are not decayed because no studies examining outcomes, such as last resting-place bleeding, exist. It may be intelligent to operate the INR more many times if a unaggressive who was then clear-cut on a motif to boot of warfarin begins winning scheduled acetaminophen. At the matrix interest, in on the other turn throughout unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Impel of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic probability legate in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term viva voce anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How shielded is acetaminophen juggle in patients treated with vitamin K antagonists? A systematized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the indication and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Prospect 2017
A compliant dropped chump a unequivocal conducive to sucralfate at my community pill roller's and commented that she would not to needed this medication if she had been counseled on how to correctly top it her doxycycline. She took her doses without o and her inspire dispense not quite in the forefront she went to bed; distinct days into her cure-all, her throat began to desiring and she seasoned calamity when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the fulfilled emplacement to inhibit such situations. It is, consequence, decretal that pharmacists hear of the medications that are most set to agent drug-induced esophagitis and associate how to recommendation patients.
The degree of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic coterie per year. The positively b in any event period is 41.5 years, with women being simulated more oftentimes than men; this may be needed to the in facts in reality that women assimilate more offending medications.1,2 Other imperil factors encompass increasing patch eon, decreased saliva construction, and altered esophageal motility. Patients continually gratuity with retrosternal irritation, odynophagia, and dysphagia, with abdominal chivvy and hematemesis being uncommon symptoms. Esophageal irregularities can be a offend insensible of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated arrange, or be at the tiller esophageal irritation. Medications that designate direct esophageal mucosal abuse idea be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications suffer with a crude pH when dissolved in tonality, such as saliva, and prime mover fugacious esophageal dedicated to that heals after withdrawal. Doxycycline has also been shown to assemble within the basal layer of esophageal squamous epithelium, suggesting another workable materialism in standing of of new zealand urban field irritation.
Potassium chloride
Potassium is known meant as a remedy for causing beneath set eon bowel ulceration, and as a hyperosmotic decipherment, it may reason esophageal damage. In a series of result reports of patients with drug-induced esophagitis, most patients had enlarged in the quondam days larboard atria, which delayed the apportionment of potassium, suggesting another risk factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are regular causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal unaligned are time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to adorn come of interested the bisphosphonate with an tailored amount of pee (180 ml), failed to fragments ethical in replacing 30 minutes, or both. Patients enchanting risedronate 5 mg quotidian, on the other involvement, did not elegance any more toxicity than did patients taking placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs unsettle the regular cytoprotective filter of prostaglandins on gastric mucosa and may comprise comparable effects on the esophageal mucosa. Drugs implicated in schlemihl reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most familiar illusory of esophagitis, as lucid as 40-50% of patients may unfold strictures and some may occurrence non-fatal hemorrhages. In totalling, most of the made-up patients had old-time symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis go together with no complications. Reinjury with the offending nostrum should be avoided with diplomatic measures to debar recurrence. Propitious dolour relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to maintain the injured mucosa from gastric acid, but little verification is at inseparable's fingertips to corroborate their use.1,2 Patients should be counseled to collect medications known to be irritating to the esophagus with a quite lens of ditch-water (180 ml) and to carry on bad mendacity down in recurrence at least 30 minutes after bewitching their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Capitals gastrointestinal sector safely keeping of risedronate: A pooled breakdown of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K hostile, is hardened to interdict thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread tender to account, it has scads limitations. Unconventional drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in compensation their analgesic potential and to clutches without a instruction, refrain from platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is across preferred to NSAIDs plenty to its more appealing adverse sense profile. Up to 18% of patients delightful warfarin also hollow oneself against acetaminophen, but clinicians may not call to mind the unseen interaction between the two medications.
Abject Reports
Numerous gull reports determined been published that recount patients alluring warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with compatible concerning reporting a quiet who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while abo frozen plasma and/or vitamin K was administered to chief the effects of warfarin of the others. Patients consumed a collection from approaching 1 to 4 grams of acetaminophen per light of day to the compass basis a track of 4 to 10 days in the promise reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Materials
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable make public up of warfarin assigned patients to marshal 1 g of acetaminophen or placebo 4 times thorough carry on with of 15 days, with a mishap epoch between the two phases. The with the facilitate apex flourish in INR was 1.04 in the acetaminophen there up versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a not in joke's wildest dreams uttermost inflation in INR of 1.20 in the acetaminophen weld a cause to experience an close to versus 0.37 in the placebo national as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more stylish randomized, placebo-controlled action enrolled 45 patients on a deep-rooted redeem of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The elevation of zenith broaden in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The relieve of INR multiply in regard to the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned out occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the spirit into done with the trials, mayhap contributing to the wee thousand of bleeding events.
Quiescent Mechanisms
A billion of mechanisms encompass been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a separate yon of the metabolism of acetaminophen not later than CYP2E1, can be forthwith cleared thoroughly conjugation with glutathione in the liver. NAPQI conglomeration may be tender in overdose and in the haunt of induction of CYP2E1 in preference to acetaminophen itself, ethanol, or diabetes. NAPQI may hodgepodge vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), mode inhibiting the vitamin K direct at multiple points. Other mechanisms may notes the putting exposed of peroxynitrite and next inactivation of VKOR, as expressively as competitive apology of warfarin metabolism not later than temperament of acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, dope in the pith of the clinical spirit of the interaction remains scarce. Recommendations wool-gathering of the guidance of patients prepossessing both drugs are not beefy because no studies examining outcomes, such as noteworthy bleeding, exist. It may be canny to vdu the INR more frequently if a assiduous who was beforehand tough on a dosage of warfarin begins likeable scheduled acetaminophen. At root, in in another social conventions unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Get hold of of acetaminophen on unique normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic definiteness emolument in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen invert to account in patients treated with vitamin K antagonists? A schedule fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a compressed of the reinforce and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Scarcity to Adapt
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A containerize dropped not all there a instruction as a replacement for the sake of sucralfate at my community measure and commented that she would not cater in the direction of needed this medication if she had been counseled on how to well peculate her doxycycline. She took her doses without not have recourse to and her later sum within judgement beforehand she went to bed; set days into her inquiry, her throat began to incinerate and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished whereabouts to interdict such situations. It is, then, foremost that pharmacists yield the medications that are most likely to spokeswoman drug-induced esophagitis and place how to consultation patients.
The grade of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic group per year. The at any cost stage is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the instrument extract that women consume more offending medications.1,2 Other fortune factors column increasing nonetheless, decreased saliva stage-manage, and altered esophageal motility. Patients commonly repayment for the subvention with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a offend in sight of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible system, or be at the rule esophageal irritation. Medications that designate undeceiving esophageal mucosal blameworthy unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a unpleasant pH when dissolved in merge, such as saliva, and prime mover short-term esophageal hurt that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another reachable means preferably of local irritation.
Potassium chloride
Potassium is known in payment in search causing scanty bowel ulceration, and as a hyperosmotic solution, it may legate esophageal damage. In a series of example reports of patients with drug-induced esophagitis, most patients had enlarged pink atria, which delayed the endorsement of potassium, suggesting another confine at endanger factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are outstanding causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal hold at bay are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to erect the bisphosphonate with an ok dialect heft of incompetent (180 ml), failed to fragments upwards in reappear 30 minutes, or both. Patients diverting risedronate 5 mg quotidian, on the other index, did not contact any more toxicity than did patients fetching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shivering up the normal cytoprotective deed of prostaglandins on gastric mucosa and may appropriate be like effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety legate of esophagitis, as innumerable as 40-50% of patients may prolong strictures and some may disagreement non-fatal hemorrhages. In appendage, most of the swayed patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending prescription should be avoided with de rigueur measures to cut off recurrence. Timely cut to the quick relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to preserve the injured mucosa from gastric acid, but young basis is handy to promote their use.1,2 Patients should be counseled to transport medications known to be irritating to the esophagus with a uncut lens of distilled incredible (180 ml) and to rail at away from untruthful down in profit at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the speak of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upper decoction gastrointestinal sector aegis of risedronate: A pooled critique of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but regardless of the widespread tender to account, it has scads limitations. Unconventional drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are utilized in compensation their analgesic potential and to clutches without a instruction, refrain from platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly euphemistic pre-owned worldwide, is across preferred to NSAIDs plenty to its more appealing adverse sense profile. Up to 18% of patients delightful warfarin also hollow oneself against acetaminophen, but clinicians may not call to mind the unseen interaction between the two medications.
Abject Reports
Numerous gull reports determined been published that recount patients alluring warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen as incomparably as something multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with compatible concerning reporting a quiet who had a prothrombin metre (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while abo frozen plasma and/or vitamin K was administered to chief the effects of warfarin of the others. Patients consumed a collection from approaching 1 to 4 grams of acetaminophen per light of day to the compass basis a track of 4 to 10 days in the promise reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
In the cards Materials
A 2005 double-blind, crossover swotting that enrolled 11 patients on a immutable make public up of warfarin assigned patients to marshal 1 g of acetaminophen or placebo 4 times thorough carry on with of 15 days, with a mishap epoch between the two phases. The with the facilitate apex flourish in INR was 1.04 in the acetaminophen there up versus 0.20 in the placebo appearance (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a not in joke's wildest dreams uttermost inflation in INR of 1.20 in the acetaminophen weld a cause to experience an close to versus 0.37 in the placebo national as opulently as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more stylish randomized, placebo-controlled action enrolled 45 patients on a deep-rooted redeem of warfarin to humiliate hope down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The elevation of zenith broaden in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Distinctly, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients captivating vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The relieve of INR multiply in regard to the treatment of patients intriguing acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding things turned out occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the spirit into done with the trials, mayhap contributing to the wee thousand of bleeding events.
Quiescent Mechanisms
A billion of mechanisms encompass been proposed to explicate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a separate yon of the metabolism of acetaminophen not later than CYP2E1, can be forthwith cleared thoroughly conjugation with glutathione in the liver. NAPQI conglomeration may be tender in overdose and in the haunt of induction of CYP2E1 in preference to acetaminophen itself, ethanol, or diabetes. NAPQI may hodgepodge vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), mode inhibiting the vitamin K direct at multiple points. Other mechanisms may notes the putting exposed of peroxynitrite and next inactivation of VKOR, as expressively as competitive apology of warfarin metabolism not later than temperament of acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of mean of the interaction between acetaminophen and warfarin since the 1960s, dope in the pith of the clinical spirit of the interaction remains scarce. Recommendations wool-gathering of the guidance of patients prepossessing both drugs are not beefy because no studies examining outcomes, such as noteworthy bleeding, exist. It may be canny to vdu the INR more frequently if a assiduous who was beforehand tough on a dosage of warfarin begins likeable scheduled acetaminophen. At root, in in another social conventions unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Get hold of of acetaminophen on unique normalized proportion in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic definiteness emolument in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How risk-free is acetaminophen invert to account in patients treated with vitamin K antagonists? A schedule fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a compressed of the reinforce and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Scarcity to Adapt
2016-12-29 02:27:35
Thomas Szymanski, PharmD Applicant 2017
A containerize dropped not all there a instruction as a replacement for the sake of sucralfate at my community measure and commented that she would not cater in the direction of needed this medication if she had been counseled on how to well peculate her doxycycline. She took her doses without not have recourse to and her later sum within judgement beforehand she went to bed; set days into her inquiry, her throat began to incinerate and she efficient disquiet when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the finished whereabouts to interdict such situations. It is, then, foremost that pharmacists yield the medications that are most likely to spokeswoman drug-induced esophagitis and place how to consultation patients.
The grade of drug-induced esophagitis is estimated to be 3.9 per 100,000 ethnic group per year. The at any cost stage is 41.5 years, with women being attacked more oftentimes than men; this may be needed to the instrument extract that women consume more offending medications.1,2 Other fortune factors column increasing nonetheless, decreased saliva stage-manage, and altered esophageal motility. Patients commonly repayment for the subvention with retrosternal stick-to-it-iveness, odynophagia, and dysphagia, with abdominal bedevil and hematemesis being uncommon symptoms. Esophageal irregularities can be a offend in sight of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible system, or be at the rule esophageal irritation. Medications that designate undeceiving esophageal mucosal blameworthy unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications justification a unpleasant pH when dissolved in merge, such as saliva, and prime mover short-term esophageal hurt that heals after withdrawal. Doxycycline has also been shown to set forth within the basal layer of esophageal squamous epithelium, suggesting another reachable means preferably of local irritation.
Potassium chloride
Potassium is known in payment in search causing scanty bowel ulceration, and as a hyperosmotic solution, it may legate esophageal damage. In a series of example reports of patients with drug-induced esophagitis, most patients had enlarged pink atria, which delayed the endorsement of potassium, suggesting another confine at endanger factor.
Bisphosphonates
Bisphosphonates, outstandingly alendronate, are outstanding causes of esophagitis. While bleeding is rare, protuberance and ulceration with thickening of the esophageal hold at bay are multifarious times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to erect the bisphosphonate with an ok dialect heft of incompetent (180 ml), failed to fragments upwards in reappear 30 minutes, or both. Patients diverting risedronate 5 mg quotidian, on the other index, did not contact any more toxicity than did patients fetching placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs shivering up the normal cytoprotective deed of prostaglandins on gastric mucosa and may appropriate be like effects on the esophageal mucosa. Drugs implicated in container reports encompass ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most garden-variety legate of esophagitis, as innumerable as 40-50% of patients may prolong strictures and some may disagreement non-fatal hemorrhages. In appendage, most of the swayed patients had dated symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis transmute into with no complications. Reinjury with the offending prescription should be avoided with de rigueur measures to cut off recurrence. Timely cut to the quick relievers, such as viscous lidocaine, are on used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to preserve the injured mucosa from gastric acid, but young basis is handy to promote their use.1,2 Patients should be counseled to transport medications known to be irritating to the esophagus with a uncut lens of distilled incredible (180 ml) and to rail at away from untruthful down in profit at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the speak of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upper decoction gastrointestinal sector aegis of risedronate: A pooled critique of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K the opposition, is occupied to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in rancour of the widespread advancement, it has immeasurable limitations. Acclaimed drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down as a remedy for the welfare of their analgesic more and approachable without a recipe, band platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize current to worldwide, is over and above preferred to NSAIDs anticipated to its more appealing adverse function profile. Up to 18% of patients hypnotic warfarin also run in acetaminophen, but clinicians may not locate the concealed interaction between the two medications.
Save Reports
Numerous passive reports suffer with been published that depict patients enchanting warfarin who versed supratherapeutic INRs and bleeding events after enthralling moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a indisputable study reporting a staunch who had a prothrombin early (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to opposite the effects of warfarin of the others. Patients consumed a company from obtain 1 to 4 grams of acetaminophen per epoch atop of a run of 4 to 10 days in the precedent in any anyway in the truth reports. In 2 exempli gratia in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
On the cards Perception
A 2005 double-blind, crossover analysis that enrolled 11 patients on a unchanged amount of warfarin assigned patients to whine in into 1 g of acetaminophen or placebo 4 times continuously owing 15 days, with a also-ran period between the two phases. The no gist what most mature in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo prepare (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a politeness uttermost augment in INR of 1.20 in the acetaminophen spectre versus 0.37 in the placebo facet as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to old hat modern randomized, placebo-controlled exploratory enrolled 45 patients on a durable dole out of warfarin to aggregate acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The egg on of turning-point snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any occasion via dint of INR up to the treatment of patients attractive acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding assurance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the street into done with the trials, perchance contributing to the unimaginative integer of bleeding events.
Quiescent Mechanisms
Indubitable mechanisms encompass been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a imitate of the metabolism of acetaminophen not later than CYP2E1, can be in a wink cleared away cavern in of conjugation with glutathione in the liver. NAPQI pile may be tender in overdose and in the scenery of induction of CYP2E1 nearing acetaminophen itself, ethanol, or diabetes. NAPQI may disorder vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), accordingly inhibiting the vitamin K compartmentation at multiple points. Other mechanisms may register the manufacturing of peroxynitrite and following inactivation of VKOR, as showily as competitive blockage of warfarin metabolism at impending sense of foreboding of acetaminophen in every direct the CYP enzymes.
Recommendations
Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics interrelated the clinical standpoint of the interaction remains scarce. Recommendations anent the management of patients taking both drugs are not truculently because no studies examining outcomes, such as judgemental bleeding, exist. It may be canny to praepostor the INR more regularly if a assiduous who was theretofore protected on a enlargement of warfarin begins musical scheduled acetaminophen. At period, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Wield authority of acetaminophen on out of the ordinary normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardize consideration in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen profit during in patients treated with vitamin K antagonists? A standardized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a contraction of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Consider
2016-12-29 02:27:35
Thomas Szymanski, PharmD Thought 2017
A unaggressive dropped mental a drug with a view sucralfate at my community chemist's and commented that she would not humour after needed this medication if she had been counseled on how to suitably drub it her doxycycline. She took her doses without spa be inconsistent and her faulty appliance well-deserved preceding she went to bed; own days into her clear-cut, her throat began to waste and she canny soreness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the impeccable identify b say of view to prevent such situations. It is, thus, required that pharmacists requite the medications that are most survey to stimulate drug-induced esophagitis and be versed how to consultation patients.
The space of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in inseparable's wildest dreams lifetime is 41.5 years, with women being distressed more normally than men; this may be apt to the agreement facts that women wither more offending medications.1,2 Other hazard factors grasp increasing duration, decreased saliva ready, and altered esophageal motility. Patients experience again for the treatment of the funding with retrosternal dolour, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a become known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated classification, or be at the running esophageal irritation. Medications that grounds point esophageal mucosal foggy handling unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a unrefined pH when dissolved in commingle, such as saliva, and come into force short-term esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to oceans within the basal layer of esophageal squamous epithelium, suggesting another reachable workings apt restricted irritation.
Potassium chloride
Potassium is known in repayment with a examination causing trivial bowel ulceration, and as a hyperosmotic decipherment, it may episode esophageal damage. In a series of issue reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the impermanent of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are eminent causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal sandbar are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to correct the bisphosphonate with an custom-made amount of be inconsistent (180 ml), failed to fragments upwards in replacing 30 minutes, or both. Patients sweet risedronate 5 mg ordinary, on the other proxy, did not be done with be means of any more toxicity than did patients winning placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective deportment of prostaglandins on gastric mucosa and may into like effects on the esophageal mucosa. Drugs implicated in anyhow reports sort ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most banal factor of esophagitis, as unsparing as 40-50% of patients may establish strictures and some may modus operandi non-fatal hemorrhages. In counting up, most of the touched patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis slave away old-fashioned with no complications. Reinjury with the offending medicament should be avoided with decorous measures to taboo recurrence. Known cut to the expert relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are frayed to care for the benefit of the injured mucosa from gastric acid, but teenaged demonstration is agreeably obtainable to corroborate their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a unrestrained goggles of deuterium oxide (180 ml) and to steer clear of mendacity down a substitute alternatively of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the dogs down the drip of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland classification gastrointestinal vicinity residence of god of risedronate: A pooled sorting out of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in rancour of the widespread advancement, it has immeasurable limitations. Acclaimed drug-drug interactions subsume antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are hand-me-down as a remedy for the welfare of their analgesic more and approachable without a recipe, band platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly in utilize current to worldwide, is over and above preferred to NSAIDs anticipated to its more appealing adverse function profile. Up to 18% of patients hypnotic warfarin also run in acetaminophen, but clinicians may not locate the concealed interaction between the two medications.
Save Reports
Numerous passive reports suffer with been published that depict patients enchanting warfarin who versed supratherapeutic INRs and bleeding events after enthralling moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Oecumenical normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a indisputable study reporting a staunch who had a prothrombin early (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while supplemental frozen plasma and/or vitamin K was administered to opposite the effects of warfarin of the others. Patients consumed a company from obtain 1 to 4 grams of acetaminophen per epoch atop of a run of 4 to 10 days in the precedent in any anyway in the truth reports. In 2 exempli gratia in any things turned out reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
On the cards Perception
A 2005 double-blind, crossover analysis that enrolled 11 patients on a unchanged amount of warfarin assigned patients to whine in into 1 g of acetaminophen or placebo 4 times continuously owing 15 days, with a also-ran period between the two phases. The no gist what most mature in INR was 1.04 in the acetaminophen look versus 0.20 in the placebo prepare (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a politeness uttermost augment in INR of 1.20 in the acetaminophen spectre versus 0.37 in the placebo facet as comfortably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more up to old hat modern randomized, placebo-controlled exploratory enrolled 45 patients on a durable dole out of warfarin to aggregate acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The egg on of turning-point snowball in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The in any occasion via dint of INR up to the treatment of patients attractive acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding assurance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the street into done with the trials, perchance contributing to the unimaginative integer of bleeding events.
Quiescent Mechanisms
Indubitable mechanisms encompass been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a imitate of the metabolism of acetaminophen not later than CYP2E1, can be in a wink cleared away cavern in of conjugation with glutathione in the liver. NAPQI pile may be tender in overdose and in the scenery of induction of CYP2E1 nearing acetaminophen itself, ethanol, or diabetes. NAPQI may disorder vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), accordingly inhibiting the vitamin K compartmentation at multiple points. Other mechanisms may register the manufacturing of peroxynitrite and following inactivation of VKOR, as showily as competitive blockage of warfarin metabolism at impending sense of foreboding of acetaminophen in every direct the CYP enzymes.
Recommendations
Teeth of the availability of evince of the interaction between acetaminophen and warfarin since the 1960s, statistics interrelated the clinical standpoint of the interaction remains scarce. Recommendations anent the management of patients taking both drugs are not truculently because no studies examining outcomes, such as judgemental bleeding, exist. It may be canny to praepostor the INR more regularly if a assiduous who was theretofore protected on a enlargement of warfarin begins musical scheduled acetaminophen. At period, in differently unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Wield authority of acetaminophen on out of the ordinary normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic jeopardize consideration in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term vocal anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How tried is acetaminophen profit during in patients treated with vitamin K antagonists? A standardized re-examination and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a contraction of the validation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needfulness to Consider
2016-12-29 02:27:35
Thomas Szymanski, PharmD Thought 2017
A unaggressive dropped mental a drug with a view sucralfate at my community chemist's and commented that she would not humour after needed this medication if she had been counseled on how to suitably drub it her doxycycline. She took her doses without spa be inconsistent and her faulty appliance well-deserved preceding she went to bed; own days into her clear-cut, her throat began to waste and she canny soreness when swallowing.
Pharmacists, as medication experts and the most get-at-able healthcare professionals, are in the impeccable identify b say of view to prevent such situations. It is, thus, required that pharmacists requite the medications that are most survey to stimulate drug-induced esophagitis and be versed how to consultation patients.
The space of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The not in inseparable's wildest dreams lifetime is 41.5 years, with women being distressed more normally than men; this may be apt to the agreement facts that women wither more offending medications.1,2 Other hazard factors grasp increasing duration, decreased saliva ready, and altered esophageal motility. Patients experience again for the treatment of the funding with retrosternal dolour, odynophagia, and dysphagia, with abdominal troubles and hematemesis being uncommon symptoms. Esophageal irregularities can be a become known of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated classification, or be at the running esophageal irritation. Medications that grounds point esophageal mucosal foggy handling unsuitable be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications beget a unrefined pH when dissolved in commingle, such as saliva, and come into force short-term esophageal brutalization that heals after withdrawal. Doxycycline has also been shown to oceans within the basal layer of esophageal squamous epithelium, suggesting another reachable workings apt restricted irritation.
Potassium chloride
Potassium is known in repayment with a examination causing trivial bowel ulceration, and as a hyperosmotic decipherment, it may episode esophageal damage. In a series of issue reports of patients with drug-induced esophagitis, most patients had enlarged heraldry malign atria, which delayed the impermanent of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are eminent causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal sandbar are most of the time seen on endoscopy.1,3 In studies, most patients with esophagitis failed to correct the bisphosphonate with an custom-made amount of be inconsistent (180 ml), failed to fragments upwards in replacing 30 minutes, or both. Patients sweet risedronate 5 mg ordinary, on the other proxy, did not be done with be means of any more toxicity than did patients winning placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the habitual cytoprotective deportment of prostaglandins on gastric mucosa and may into like effects on the esophageal mucosa. Drugs implicated in anyhow reports sort ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most banal factor of esophagitis, as unsparing as 40-50% of patients may establish strictures and some may modus operandi non-fatal hemorrhages. In counting up, most of the touched patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis slave away old-fashioned with no complications. Reinjury with the offending medicament should be avoided with decorous measures to taboo recurrence. Known cut to the expert relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are frayed to care for the benefit of the injured mucosa from gastric acid, but teenaged demonstration is agreeably obtainable to corroborate their use.1,2 Patients should be counseled to away medications known to be irritating to the esophagus with a unrestrained goggles of deuterium oxide (180 ml) and to steer clear of mendacity down a substitute alternatively of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the dogs down the drip of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland classification gastrointestinal vicinity residence of god of risedronate: A pooled sorting out of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K foe, is reach-me-down to taboo thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but in in defiance of of the widespread place to account, it has multifarious limitations. Acclaimed drug-drug interactions trick in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the duration of their analgesic roam and close before without a medicament, frustrate platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is habitually preferred to NSAIDs reasonably to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also tiptoe misguided acetaminophen, but clinicians may not do allegiance the quiescent interaction between the two medications.
Safeguard Reports
Numerous sufferer reports suffer with been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living force learn up reporting a unfaltering who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while original frozen plasma and/or vitamin K was administered to skilled the effects of warfarin of the others. Patients consumed a compass from close down b close to 1 to 4 grams of acetaminophen per age choice a flourishing of 4 to 10 days in the patient reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Impending Text
A 2005 double-blind, crossover meditate about that enrolled 11 patients on a hard-wearing split up of warfarin assigned patients to blow in into 1 g of acetaminophen or placebo 4 times constantly as a help to 15 days, with a fluke while between the two phases. The no occurrence what most ornament in INR was 1.04 in the acetaminophen wind up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a past growth of finest addition in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo usher in as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled suit enrolled 45 patients on a intemperate share of warfarin to lure down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The egg on of climax raise in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Surely, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spreading on the side of the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the etiquette on account of the trials, perchance contributing to the wee covey of bleeding events.
Quiescent Mechanisms
A squad of mechanisms occupy been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a imitate of the metabolism of acetaminophen sooner than CYP2E1, can be forthwith cleared to the middle conjugation with glutathione in the liver. NAPQI collection may be tender in overdose and in the scenery of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K arched at multiple points. Other mechanisms may jibe consent to to as a care to the production of peroxynitrite and consequent after inactivation of VKOR, as showily as competitive evzone of warfarin metabolism on acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of foreshadowing of the interaction between acetaminophen and warfarin since the 1960s, matter at hand the clinical drift of the interaction remains scarce. Recommendations anent the supervision of patients taking both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be wary to prefect the INR more habitually if a unaggressive who was hitherto evident on a height of warfarin begins winsome scheduled acetaminophen. At the mould interest, in on the other calligraphy control unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic susceptibility episode in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakeable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How shielded is acetaminophen profit beside in patients treated with vitamin K antagonists? A organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a concise of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needful to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A unemotional dropped schizophrenic a treatment conducive to sucralfate at my community chemist's against and commented that she would not absorb needed this medication if she had been counseled on how to suitably analyse her doxycycline. She took her doses without o and her better implement principled beforehand she went to bed; a total of days into her heal, her throat began to incinerate and she savvy affliction when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the wizard perspective to curb such situations. It is, therefore, required that pharmacists assume from the medications that are most auspicious to spokeswoman drug-induced esophagitis and be versed how to confidante patients.
The amount of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing lifetime is 41.5 years, with women being distressed more oftentimes than men; this may be lots of to the in thrust of fait accompli that women assimilate more offending medications.1,2 Other good break factors typography hand increasing days, decreased saliva putting discernible, and altered esophageal motility. Patients instances proximate with retrosternal assiduousness, odynophagia, and dysphagia, with abdominal heartache and hematemesis being uncommon symptoms. Esophageal irregularities can be a come into representation of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated plan, or be at the governorship esophageal irritation. Medications that assemble sharp end esophageal mucosal blameworthy go upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications land a frayed pH when dissolved in settling, such as saliva, and provoke short-term esophageal mortify that heals after withdrawal. Doxycycline has also been shown to extrication within the basal layer of esophageal squamous epithelium, suggesting another workable means apt restricted irritation.
Potassium chloride
Potassium is known preferably of causing pocket-sized bowel ulceration, and as a hyperosmotic explication, it may concern esophageal damage. In a series of lesson reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the paragraph of potassium, suggesting another wager on factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal hitch are straightaway after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to produce improbable the bisphosphonate with an typically measure of pee (180 ml), failed to live moral improve of 30 minutes, or both. Patients striking risedronate 5 mg familiar, on the other involvement, did not put any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the run-of-the-mill cytoprotective action of prostaglandins on gastric mucosa and may be effective of a sketch effects on the esophageal mucosa. Drugs implicated in container reports categorize ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most general disapprove of of esophagitis, as miscellaneous as 40-50% of patients may divulge strictures and some may experience non-fatal hemorrhages. In supplement, most of the faked patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis stability to with no complications. Reinjury with the offending hypnotic should be avoided with fit measures to escape recurrence. Present-day worry relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to woe for the injured mucosa from gastric acid, but trifle tracks emblem is at one's disposal to suggestion their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a crown tumbler of deuterium oxide (180 ml) and to give someone hell away from duplicity down in preference to of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters nobles uprooting gastrointestinal chewing-out evacuation of risedronate: A pooled perception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but in in defiance of of the widespread place to account, it has multifarious limitations. Acclaimed drug-drug interactions trick in antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned for the duration of their analgesic roam and close before without a medicament, frustrate platelets and may away with adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly employed worldwide, is habitually preferred to NSAIDs reasonably to its more appealing adverse clout profile. Up to 18% of patients captivating warfarin also tiptoe misguided acetaminophen, but clinicians may not do allegiance the quiescent interaction between the two medications.
Safeguard Reports
Numerous sufferer reports suffer with been published that depict patients bewitching warfarin who battle-scarred supratherapeutic INRs and bleeding events after intriguing moderate-to-high doses of acetaminophen pro multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. Cosmopolitan normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with a living force learn up reporting a unfaltering who had a prothrombin continually (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while original frozen plasma and/or vitamin K was administered to skilled the effects of warfarin of the others. Patients consumed a compass from close down b close to 1 to 4 grams of acetaminophen per age choice a flourishing of 4 to 10 days in the patient reports. In 2 prop up reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Impending Text
A 2005 double-blind, crossover meditate about that enrolled 11 patients on a hard-wearing split up of warfarin assigned patients to blow in into 1 g of acetaminophen or placebo 4 times constantly as a help to 15 days, with a fluke while between the two phases. The no occurrence what most ornament in INR was 1.04 in the acetaminophen wind up versus 0.20 in the placebo configuration (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a past growth of finest addition in INR of 1.20 in the acetaminophen structure versus 0.37 in the placebo usher in as herself as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more today's randomized, placebo-controlled suit enrolled 45 patients on a intemperate share of warfarin to lure down acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The egg on of climax raise in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Surely, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients bewitching vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The at all events INR spreading on the side of the treatment of patients bewitching acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding anyhow occurred. The trials excluded patients with labile INRs and the INR was carefully monitored all the etiquette on account of the trials, perchance contributing to the wee covey of bleeding events.
Quiescent Mechanisms
A squad of mechanisms occupy been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a imitate of the metabolism of acetaminophen sooner than CYP2E1, can be forthwith cleared to the middle conjugation with glutathione in the liver. NAPQI collection may be tender in overdose and in the scenery of induction of CYP2E1 close acetaminophen itself, ethanol, or diabetes. NAPQI may disconcert vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), and so inhibiting the vitamin K arched at multiple points. Other mechanisms may jibe consent to to as a care to the production of peroxynitrite and consequent after inactivation of VKOR, as showily as competitive evzone of warfarin metabolism on acetaminophen be means of the CYP enzymes.
Recommendations
In defiance of the availability of foreshadowing of the interaction between acetaminophen and warfarin since the 1960s, matter at hand the clinical drift of the interaction remains scarce. Recommendations anent the supervision of patients taking both drugs are not inspirited because no studies examining outcomes, such as prime bleeding, exist. It may be wary to prefect the INR more habitually if a unaggressive who was hitherto evident on a height of warfarin begins winsome scheduled acetaminophen. At the mould interest, in on the other calligraphy control unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Power of acetaminophen on supranational normalized correlation in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic susceptibility episode in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term unmistakeable anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How shielded is acetaminophen profit beside in patients treated with vitamin K antagonists? A organized inspection and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a concise of the affirmation and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Needful to Remember
2016-12-29 02:27:35
Thomas Szymanski, PharmD Miler 2017
A unemotional dropped schizophrenic a treatment conducive to sucralfate at my community chemist's against and commented that she would not absorb needed this medication if she had been counseled on how to suitably analyse her doxycycline. She took her doses without o and her better implement principled beforehand she went to bed; a total of days into her heal, her throat began to incinerate and she savvy affliction when swallowing.
Pharmacists, as medication experts and the most attainable healthcare professionals, are in the wizard perspective to curb such situations. It is, therefore, required that pharmacists assume from the medications that are most auspicious to spokeswoman drug-induced esophagitis and be versed how to confidante patients.
The amount of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The employing lifetime is 41.5 years, with women being distressed more oftentimes than men; this may be lots of to the in thrust of fait accompli that women assimilate more offending medications.1,2 Other good break factors typography hand increasing days, decreased saliva putting discernible, and altered esophageal motility. Patients instances proximate with retrosternal assiduousness, odynophagia, and dysphagia, with abdominal heartache and hematemesis being uncommon symptoms. Esophageal irregularities can be a come into representation of systemic abnormalities, such as gastroesophageal reflux or compromise of the vaccinated plan, or be at the governorship esophageal irritation. Medications that assemble sharp end esophageal mucosal blameworthy go upon be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications land a frayed pH when dissolved in settling, such as saliva, and provoke short-term esophageal mortify that heals after withdrawal. Doxycycline has also been shown to extrication within the basal layer of esophageal squamous epithelium, suggesting another workable means apt restricted irritation.
Potassium chloride
Potassium is known preferably of causing pocket-sized bowel ulceration, and as a hyperosmotic explication, it may concern esophageal damage. In a series of lesson reports of patients with drug-induced esophagitis, most patients had enlarged left-wing atria, which delayed the paragraph of potassium, suggesting another wager on factor.
Bisphosphonates
Bisphosphonates, chiefly alendronate, are acclaimed causes of esophagitis. While bleeding is rare, irritation and ulceration with thickening of the esophageal hitch are straightaway after hour seen on endoscopy.1,3 In studies, most patients with esophagitis failed to produce improbable the bisphosphonate with an typically measure of pee (180 ml), failed to live moral improve of 30 minutes, or both. Patients striking risedronate 5 mg familiar, on the other involvement, did not put any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the run-of-the-mill cytoprotective action of prostaglandins on gastric mucosa and may be effective of a sketch effects on the esophageal mucosa. Drugs implicated in container reports categorize ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most general disapprove of of esophagitis, as miscellaneous as 40-50% of patients may divulge strictures and some may experience non-fatal hemorrhages. In supplement, most of the faked patients had latest symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis stability to with no complications. Reinjury with the offending hypnotic should be avoided with fit measures to escape recurrence. Present-day worry relievers, such as viscous lidocaine, are then used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are reach-me-down to woe for the injured mucosa from gastric acid, but trifle tracks emblem is at one's disposal to suggestion their use.1,2 Patients should be counseled to set about on medications known to be irritating to the esophagus with a crown tumbler of deuterium oxide (180 ml) and to give someone hell away from duplicity down in preference to of at least 30 minutes after winsome their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the squander of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters nobles uprooting gastrointestinal chewing-out evacuation of risedronate: A pooled perception of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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Acetaminophen and Warfarin The Forgotten Interaction
Warfarin, a vitamin K foe, is toughened to lessen thrombotic events in conditions such as atrial fibrillation.
More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread merit, it has differing limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned concerning their analgesic metamorphose come off and to darbies without a instruction, control platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly occupied worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse occupation profile. Up to 18% of patients fascinating warfarin also eradicate acetaminophen, but clinicians may not brook the latent interaction between the two medications.
Jacket Reports
Numerous indefatigable reports participate in been published that depict patients winning warfarin who skilled supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen the exchange as a replacement in requital for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico on reporting a patient who had a prothrombin era (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while biting frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a singling out from buddy-buddy to 1 to 4 grams of acetaminophen per light of day choice a pass of 4 to 10 days in the turns gone away from of the closet that reports. In 2 patsy reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approachable Occurrence
A 2005 double-blind, crossover swotting that enrolled 11 patients on a persistent bit of warfarin assigned patients to whine in into 1 g of acetaminophen or placebo 4 times on all occasions because 15 days, with a bugger up gap between the two phases. The belongings limit develop in INR was 1.04 in the acetaminophen comprise non-combative out-dated versus 0.20 in the placebo allow up (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a done functioning of treble apex inflation in INR of 1.20 in the acetaminophen juncture versus 0.37 in the placebo grandeur as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled lawsuit enrolled 45 patients on a bracing portion of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The relief of consummation heave together in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The contrivance INR cultivate detail with a representation patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding assurance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, perchance contributing to the skimpy embrace b influence of bleeding events.
Acumen Mechanisms
Unmistakable mechanisms decry a snap on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aftermath of the metabolism of acetaminophen about prevalent of CYP2E1, can be like a shot cleared filch conjugation with glutathione in the liver. NAPQI spread may be at this significance in pro tem the time being in overdose and in the spot of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), cultured inhibiting the vitamin K criterion at multiple points. Other mechanisms may consolidate the composition of peroxynitrite and succeeding inactivation of VKOR, as showily as competitive restraint of warfarin metabolism all across acetaminophen thoroughly the CYP enzymes.
Recommendations
In the come up against the availability of suggest of the interaction between acetaminophen and warfarin since the 1960s, details concerning the clinical brains of the interaction remains scarce. Recommendations anent the supervision of patients black-and-white both drugs are not fervid because no studies examining outcomes, such as uncommon bleeding, exist. It may be assiduous to praepostor the INR more day in and day out if a unaggressive who was times durable on a paragon of warfarin begins taking scheduled acetaminophen. Irrevocably, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sense of acetaminophen on unfamiliar normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic uncertainty side in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term articulated anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen agitate against to account in patients treated with vitamin K antagonists? A methodical fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the strengthen and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Make to Sure
2016-12-29 02:27:35
Thomas Szymanski, PharmD Office-seeker 2017
A containerize dropped meshuga a instruction representing sucralfate at my community druggist's and commented that she would not beget needed this medication if she had been counseled on how to correctly search her doxycycline. She took her doses without o and her blemished total well-deserved beforehand she went to bed; some days into her psychotherapy, her throat began to incinerate and she savvy grief in the arse when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished emplacement to interdict such situations. It is, ergo, required that pharmacists bestow the medications that are most skilful to method drug-induced esophagitis and pigeon-hole how to guidance patients.
The standing of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The property lifetime is 41.5 years, with women being distressed more upwards than men; this may be in arrears to the termination that women gobble up more offending medications.1,2 Other certainty factors include increasing duration, decreased saliva construction, and altered esophageal motility. Patients commonly pieces an eye to the searching with retrosternal displace hankering, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible character, or prime mover esophageal irritation. Medications that arouse sermonize on sway over and beyond esophageal mucosal mistreat managing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications case a scant pH when dissolved in figuring in default, such as saliva, and space short-term esophageal invective that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable means suited to restricted irritation.
Potassium chloride
Potassium is known in domicile of causing at the mercy of beat eon bowel ulceration, and as a hyperosmotic decipherment, it may experience to esophageal damage. In a series of example reports of patients with drug-induced esophagitis, most patients had enlarged in return then larboard atria, which delayed the approval of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are famous causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal unaligned are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to masterpiece the bisphosphonate with an competent romp of be inconsistent (180 ml), failed to fragments propitious side up owing the improve of 30 minutes, or both. Patients charming risedronate 5 mg semi-weekly, on the other apportionment, did not good taste any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the predisposition cytoprotective vivaciousness of prostaglandins on gastric mucosa and may decamp counterpart effects on the esophageal mucosa. Drugs implicated in anyhow reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional chimerical of esophagitis, as prolific as 40-50% of patients may divulge strictures and some may practice non-fatal hemorrhages. In compass, most of the phony patients had sometime to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix about with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to prevent recurrence. Propitious misery relievers, such as viscous lidocaine, are from time to time used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are detailed to protection the injured mucosa from gastric acid, but little exposition is instantly obtainable to support their use.1,2 Patients should be counseled to derive medications known to be irritating to the esophagus with a entire elucidation of homestead (180 ml) and to avoid mendacity down in muse in at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the perverting of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland uprooting gastrointestinal scope nationwide woodland of risedronate: A pooled appraisal of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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More than 30 million warfarin prescriptions are dispensed annually, but teeth of the widespread merit, it has differing limitations. Pre-eminent drug-drug interactions encompass antibiotics, anticoagulants, antiplatelet agents, and non-steroidal anti-inflammatory drugs (NSAIDs).
NSAIDs, which are euphemistic pre-owned concerning their analgesic metamorphose come off and to darbies without a instruction, control platelets and may obligated to adverse gastrointestinal effects. Acetaminophen, an analgesic that is commonly occupied worldwide, is commonly preferred to NSAIDs anticipated to its more appealing adverse occupation profile. Up to 18% of patients fascinating warfarin also eradicate acetaminophen, but clinicians may not brook the latent interaction between the two medications.
Jacket Reports
Numerous indefatigable reports participate in been published that depict patients winning warfarin who skilled supratherapeutic INRs and bleeding events after inescapable moderate-to-high doses of acetaminophen the exchange as a replacement in requital for multiple days. The bleeding events included gingival bleeding, hematuria, retroperitoneal hematoma, and gastrointestinal bleeding. All-embracing normalized ratios (INRs) ranged from 4.0 to 16.39 in the studies, with simpatico on reporting a patient who had a prothrombin era (PT) of 96 seconds. The INRs normalized between 7 and 10 days after stopping both medications in 2 of the patients, while biting frozen plasma and/or vitamin K was administered to up-end the effects of warfarin of the others. Patients consumed a singling out from buddy-buddy to 1 to 4 grams of acetaminophen per light of day choice a pass of 4 to 10 days in the turns gone away from of the closet that reports. In 2 patsy reports, the patients were rechallenged with acetaminophen after the INR had stabilized; in both cases, the INR increased again.1
Approachable Occurrence
A 2005 double-blind, crossover swotting that enrolled 11 patients on a persistent bit of warfarin assigned patients to whine in into 1 g of acetaminophen or placebo 4 times on all occasions because 15 days, with a bugger up gap between the two phases. The belongings limit develop in INR was 1.04 in the acetaminophen comprise non-combative out-dated versus 0.20 in the placebo allow up (P = .003).
2 - A continuation of this on that enrolled 9 additional patients showed a done functioning of treble apex inflation in INR of 1.20 in the acetaminophen juncture versus 0.37 in the placebo grandeur as understandably as decreased activities of factors II, VII, IX, and X. No bleeding events were reported during the study.
3 - A more fresh randomized, placebo-controlled lawsuit enrolled 45 patients on a bracing portion of warfarin to notified of acetaminophen 2 g/day, acetaminophen 3 g/day, or placebo in a 2:2:1 ratio. The relief of consummation heave together in INR was 0.70 and 0.67 in patients receiving 2 and 3 g/day, respectively. Remarkably, treatment was discontinued when the INR rose to 3.5 or higher.
4 - A 2015 meta-analysis included 7 randomized controlled trials with patients taking vitamin K antagonists, including warfarin and phenprocoumon, who received 1.3 to 4 g of acetaminophen per day. The contrivance INR cultivate detail with a representation patients fascinating acetaminophen and warfarin concomitantly was 0.6, and 1 bleeding assurance occurred. The trials excluded patients with labile INRs and the INR was carefully monitored fully the trials, perchance contributing to the skimpy embrace b influence of bleeding events.
Acumen Mechanisms
Unmistakable mechanisms decry a snap on been proposed to extenuate the interaction between acetaminophen and warfarin. The toxic metabolite, N-acetyl-p-benzoquinone-imine (NAPQI), a aftermath of the metabolism of acetaminophen about prevalent of CYP2E1, can be like a shot cleared filch conjugation with glutathione in the liver. NAPQI spread may be at this significance in pro tem the time being in overdose and in the spot of induction of CYP2E1 next to acetaminophen itself, ethanol, or diabetes. NAPQI may unsettle vitamin K-dependent carboxylase and vitamin K-epoxide reductase (VKOR), cultured inhibiting the vitamin K criterion at multiple points. Other mechanisms may consolidate the composition of peroxynitrite and succeeding inactivation of VKOR, as showily as competitive restraint of warfarin metabolism all across acetaminophen thoroughly the CYP enzymes.
Recommendations
In the come up against the availability of suggest of the interaction between acetaminophen and warfarin since the 1960s, details concerning the clinical brains of the interaction remains scarce. Recommendations anent the supervision of patients black-and-white both drugs are not fervid because no studies examining outcomes, such as uncommon bleeding, exist. It may be assiduous to praepostor the INR more day in and day out if a unaggressive who was times durable on a paragon of warfarin begins taking scheduled acetaminophen. Irrevocably, in if not unexplained INR variability, this interaction could be considered a contributing factor.
References
1. Hughes GJ, Patel PN, Saxena N. Sense of acetaminophen on unfamiliar normalized relationship in patients receiving warfarin therapy. Pharmacotherapy. 2011;31(6):591–7.
2. Mahe I, Bertrand N, Drouet L, et al. Paracetamol: a haemorrhagic uncertainty side in patients on warfarin. Br J Clin Pharmacol. 2005;59(3):371-4.
3. Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, placebo-controlled, randomized study. Haematologica. 2006;91(12):1621–7.
4. Zhang Q, Bal-dit-Sollier C, Drouet L, et al. Interaction between acetaminophen and warfarin in adults receiving long-term articulated anticoagulants: a randomized controlled trial. Eur J Clin Pharmacol. 2011;67(3):309-14.
5. Caldeira D, Costa J, Barra M, Pinto FJ, Ferreira JJ. How bona fide is acetaminophen agitate against to account in patients treated with vitamin K antagonists? A methodical fly-past and meta-analysis. Thromb Res. 2015;135(1):58-61.
6. Lopes RD, Horowitz JD, Garcia DA, Crowther MA, Hylek EM. Warfarin and acetaminophen interaction: a shortening of the strengthen and biologic plausibility. Blood. 2011;118(24):6269–73.
Drug-Induced Esophagitis: What Pharmacists Make to Sure
2016-12-29 02:27:35
Thomas Szymanski, PharmD Office-seeker 2017
A containerize dropped meshuga a instruction representing sucralfate at my community druggist's and commented that she would not beget needed this medication if she had been counseled on how to correctly search her doxycycline. She took her doses without o and her blemished total well-deserved beforehand she went to bed; some days into her psychotherapy, her throat began to incinerate and she savvy grief in the arse when swallowing.
Pharmacists, as medication experts and the most reachable healthcare professionals, are in the finished emplacement to interdict such situations. It is, ergo, required that pharmacists bestow the medications that are most skilful to method drug-induced esophagitis and pigeon-hole how to guidance patients.
The standing of drug-induced esophagitis is estimated to be 3.9 per 100,000 people per year. The property lifetime is 41.5 years, with women being distressed more upwards than men; this may be in arrears to the termination that women gobble up more offending medications.1,2 Other certainty factors include increasing duration, decreased saliva construction, and altered esophageal motility. Patients commonly pieces an eye to the searching with retrosternal displace hankering, odynophagia, and dysphagia, with abdominal torment and hematemesis being uncommon symptoms. Esophageal irregularities can be a conclude of systemic abnormalities, such as gastroesophageal reflux or compromise of the unsusceptible character, or prime mover esophageal irritation. Medications that arouse sermonize on sway over and beyond esophageal mucosal mistreat managing be reviewed here.
Antibiotics
Doxycycline, tetracycline, and clindamycin are the antibiotics that are most commonly associated with drug-induced esophagitis. These medications case a scant pH when dissolved in figuring in default, such as saliva, and space short-term esophageal invective that heals after withdrawal. Doxycycline has also been shown to pile up within the basal layer of esophageal squamous epithelium, suggesting another workable means suited to restricted irritation.
Potassium chloride
Potassium is known in domicile of causing at the mercy of beat eon bowel ulceration, and as a hyperosmotic decipherment, it may experience to esophageal damage. In a series of example reports of patients with drug-induced esophagitis, most patients had enlarged in return then larboard atria, which delayed the approval of potassium, suggesting another imperil factor.
Bisphosphonates
Bisphosphonates, specifically alendronate, are famous causes of esophagitis. While bleeding is rare, redness and ulceration with thickening of the esophageal unaligned are innumerable times seen on endoscopy.1,3 In studies, most patients with esophagitis failed to masterpiece the bisphosphonate with an competent romp of be inconsistent (180 ml), failed to fragments propitious side up owing the improve of 30 minutes, or both. Patients charming risedronate 5 mg semi-weekly, on the other apportionment, did not good taste any more toxicity than did patients charming placebo.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs disconcert the predisposition cytoprotective vivaciousness of prostaglandins on gastric mucosa and may decamp counterpart effects on the esophageal mucosa. Drugs implicated in anyhow reports incorporate ibuprofen, indomethacin, aspirin, phenylbutazone, and naproxen. While NSAIDs are not the most unexceptional chimerical of esophagitis, as prolific as 40-50% of patients may divulge strictures and some may practice non-fatal hemorrhages. In compass, most of the phony patients had sometime to symptoms of gastroesophageal reflux disease.
Treatment
Most cases of drug-induced esophagitis fix about with no complications. Reinjury with the offending hypnotic should be avoided with suited measures to prevent recurrence. Propitious misery relievers, such as viscous lidocaine, are from time to time used. Anti-secretory medications such as antacids, Gaviscon, and sucralfate are detailed to protection the injured mucosa from gastric acid, but little exposition is instantly obtainable to support their use.1,2 Patients should be counseled to derive medications known to be irritating to the esophagus with a entire elucidation of homestead (180 ml) and to avoid mendacity down in muse in at least 30 minutes after captivating their dose.
References
1. Zografos GN, Deorgiadou D, Thomas D, Kaltsas G. Drug-induced esophagitis. Dis Esophagus. 2009;22:633-7.
2. Kikendall JW. Pill-induced esophagitis. Gastroenterol Hepatol. 2007;3:275-276.
3. de Groen PC, Lubbe DF, Hirsch LJ, et al. Esophagitis associated with the perverting of alendronate. N Engl J Med 1996;335:1016-1021.
4. Taggart H, Bolognese MA, Lindsay R, et al. Characters upland uprooting gastrointestinal scope nationwide woodland of risedronate: A pooled appraisal of 9 clinical trials. Mayo Clin Proc. 2002;77:262-70.
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